Conquest: Spring 2007 by MD Anderson Cancer Center

CONQUEST S

V O L U M E

2 1

I S S U E

Three Women, One Mission â&#x20AC;&#x201C; to Help Save Lives

M I S S I O N The mission of The University of Texas M. D. Anderson Cancer Center is to eliminate cancer in Texas, the nation, and the world through outstanding programs that integrate patient care, research and prevention, and through education for undergraduate and graduate students, trainees, professionals, employees and the public.

V I S I O N We shall be the premier cancer center in the world, based on the excellence of our people, our research-driven patient care and our science. We are Making Cancer History.

C O R E

VA L U E S Caring

By our words and actions, we create a caring environment for everyone.

Integrity We work together to merit the trust of our colleagues and those we serve.

Discovery We embrace creativity and seek new knowledge. On the Cover: Ovarian cancer survivors (from left) Mary Glenn Rice, Kim Podraza and Judith Buelow are encouraging women to become more aware of the symptoms associated with the disease in hopes of saving lives.

Check out the Conquest Web site at w w w. m d a n d e r s o n . o r g / c o n q u e s t

CONTENTS C O N Q U E S T

SPRING 2007

2 FRONTLINE Anti-Allergy Drug Reduces Tumor Growth

F E AT U R E S

4 19

OVARIAN CANCER —

PROFILE

A FORCE TO BE RECKONED WITH

Melissa L. Bondy, Ph.D. Although the rate of ovarian cancer has decreased slightly, the ratio of deaths to new cases has remained virtually unchanged.

Unrelenting as this disease often can be, it’s now coming up CANCER BRIEFINGS against a force that looks towards its elimination. Partner to the South Letter of Intent Postdocs Speak Out

10 BRINGING TUMORS INTO SHARPER VIEW

MOVING FORWARD Adolfo Sosa

When asked what is making molecular imaging possible, M. D. Anderson radiologists point to “fusion imaging,” which is allowing them to better characterize and localize tumors and assess drug activity.

16 PROGRESS AGAINST CANCER

Gabriel N. Hortobagyi, M.D., speaks on the recent decline in cancer death rates despite a growing and rapidly aging population and the need for sustained funding to assure continued progress against the disease.

CONQUEST SPRING 2007

FRONTLINE A SURPRISING FIND: ANTI-ALLERGY DRUG REDUCES TUMOR GROWTH C

raig Logsdon’s five-year search for an agent to treat pancreatic cancer may be nearing an end. A common anti-allergy drug might hold the essential properties needed to destroy this aggressive type of tumor. In the Journal of the National Cancer Institute, Logsdon and his team report that combining the drug cromolyn with chemotherapy was nearly three times better at retarding growth of human pancreatic tumors in mice compared to the chemotherapy agent gemcitabine alone. The finding may lead to a new treatment for patients with pancreatic cancer, which is believed to be the most lethal of all cancers. More than 95 percent of patients diagnosed with the disease die from it, and one-half of those deaths occur in the first six months after diagnosis. “Our goal is to offer longer life to these patients, and the combination of these two agents may well do that,” says Logsdon, Ph.D., professor in the Department of Cancer Biology and the study’s lead author. According to Logsdon, the cromolyn-gemcitabine combination reduced pancreatic cancer growth in mice by 85 percent compared to the control group. Cromolyn also had a good effect on its own, reducing tumor growth by 70 percent as opposed to 50 percent when gemcitabine was used alone. “Cromolyn seems to reduce survival mechanisms in pancreatic cancer cells enough that when gemcitabine is added, the chemotherapy is more effective,” Logsdon says. “This is good because chemotherapy normally has very little effect in these patients.”

A TWIST OF FATE The relationship between how cromolyn controls allergies and its anti-tumor effect in pancreatic cancer remains unclear. However, Logsdon discovered that cromolyn can bind to a specific protein produced by cancer cells and block that protein’s ability to interact with a receptor that stimulates cancer cell growth, survival and spread. “Through serendipity and basic science sleuthing, we may now have something that helps patients,” Logsdon says. Logsdon explains that he searched for genes that produced proteins secreted only by cancer cells, which would then loop around and act on the cancer cell through a receptor on the cell surface. “That way, we could have two potential targets — the secreted protein and the receptor.” After slogging through dozens of potential genes, Logsdon fixed his attention on the protein S100P and found that it was highly specific to pancreatic cancer. It was not found in normal pancreatic cells.

Craig Logsdon, Ph.D. (left), and Senior Research Scientist Thiru Arumugam, Ph.D., found that combining an anti-allergy drug with chemotherapy was significantly better at slowing the growth of human pancreatic tumors implanted in mice compared to using chemotherapy alone.

Using gene-silencing techniques, Logsdon further discovered that when the protein S100P is disabled, cancer growth is slowed. “S100P plays a role in tumor development because it causes cancer cells to grow faster, survive better and become more invasive,” he notes. Logsdon found that S100P interacts with a receptor known as RAGE, which also plays a role in diabetes, arthritis and Alzheimer’s disease. If RAGE is blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor doesn’t accelerate growth. While Logsdon was defining S100P in pancreatic cancer, a Japanese research team working on allergies ran an experiment to see which proteins “stuck” to cromolyn and other anti-allergy drugs. Several members of the S100 gene family, including S100P, did. Based on these findings, Logsdon then applied cromolyn to pancreatic cancer cell lines and found that tumor growth slowed. A larger effect was seen when the chemotherapy agent gemcitabine was combined with cromolyn.

THINKING AHEAD Logsdon suspects that cromolyn may have other anti-tumor effects, a theory which he is currently testing. “For me this is pretty thrilling,” he says. “In a relatively short time, we have gone all the way from discovering a molecule to preparations for a clinical trial.” Although cromolyn is off-patent and widely available, it has been used only as a topical agent (through an inhaler, nasal spray and eye drops), so the research team is studying how to deliver the drug internally. The study was funded by the Lockton Endowment and M. D. Anderson’s pancreatic Specialized Programs of Research Excellence grant. — Scott Merville

Mary Glenn Rice, Kim Podraza, Judith Buelow. Three women, one diagnosis – ovarian cancer.

O VA R I A N

CANCER “I

was shocked. A cancer diagnosis was the furthest

thing from my mind,” says Rice, who learned she had stage IIIC ovarian cancer. Ditto for Podraza, who was diagnosed with a stage III mixed germ cell tumor, a rare form of the disease accounting for only 3 percent to 5 percent of all ovarian cancers. For Buelow, she couldn’t believe the grapefruit-sized tumor in her belly was real. “I kept thinking I’m going to wake up and realize this all has been a big nightmare.” But it wasn’t. Buelow, too, had advanced ovarian cancer. She thought, “Well, this may be it.”

A Force to be Reckoned With by Eileen A. Ellig

Although (from left) Mary Glenn Rice, Kim Podraza and Judith Buelow, don’t know each other, they share two things in common — a diagnosis of ovarian cancer and a mission to help others overcome the disease.

A FORCE TO BE RECKONED WITH “Unrelenting” best describes ovarian cancer’s hold on the more than 22,000 women who are diagnosed with the disease every year. Although the rate of ovarian cancer has decreased slightly, the ratio of deaths to new cases has remained virtually unchanged for decades, with three-fourths of women ultimately succumbing to the disease. Rice, Podraza and Buelow are the exceptions. Each now has been cancer free for six, 23 and 18 years, respectively. The reason why a significant shift in survival has yet to occur is because ovarian tumors escape early detection and evade the killing effects of anti-cancer agents. Aside from the fact that there is not any reliable way to mass screen women for the disease, ovarian tumors get a little help from Mother Nature. The very positioning of the ovaries makes it difficult to detect developing ovarian tumors early. About the size and shape of an almond, the ovaries flank each side of the uterus and are embedded deep in the lower abdomen. As a result, ovarian cancer typically is not detected until its late stages because, when early symptoms appear, they often mimic other more common ailments, according to David Gershenson, M.D., chair of the Department of Gynecologic Oncology. This is the case for nearly 75 percent of all women who are diagnosed with the disease.

“At the time, I had a lot of symptoms that most women with the disease have but tend to overlook until they get to be too much,” says Podraza, who thought a simple prescription from her doctor could cure all her ills — bloating, indigestion and intermittent bouts of constipation and diarrhea. Least of all did she suspect she would need emergency surgery, which revealed two large tumors, one on each ovary. Although the majority of women respond to postoperative chemotherapy, most relapse within a year because their tumors progress or recur, Gershenson notes. Initially taken down by the onslaught of chemotherapy, ovarian tumors often become resistant to therapy by turning on specific growth factors, or proteins, which promote survival. Clever as they may be, ovarian tumors are now coming up against a force that looks toward their elimination. Nearly 50 members strong, the Blanton-Davis Ovarian Cancer Research Program team is deep into the search for answers to ovarian cancer. TURNING DISCOVERIES INTO SOLUTIONS Ovarian cancer is a complex disease, characterized by many genetic and molecular abnormalities — some of which are known, others that are yet to be uncovered. Although the majority of ovarian cancers are considered sporadic, occurring because of a chance combination of many

O VA R I A N C A N C E R — A F O R C E T O B E R E C K O N E D W I T H

David Gershenson, M.D., and his team are deep into the search for answers to ovarian cancer, a disease that affects more than 22,000 women every year.

different factors, 5 percent to 10 percent of cases are associated with an alteration in one of two genes — BRCA1 or BRCA2 — that are passed down from generation to generation. With increasing knowledge of these and other genes responsible for tumor growth and progression, investigators are testing to see whether any of these abnormalities are good targets for therapy or viable markers for screening and prevention. While targeting specific genes in tumors is an ongoing approach, investigators also are looking to the tumor microenvironment for answers. “By nature, ovarian tumors are genetically unstable and can evolve and become resistant to therapy,” says Anil Sood, M.D., professor in the Department of Gynecologic Oncology. “The cells surrounding them, however, tend to be more stable and potentially better targets.” Specifically, investigators are focusing on the vascular endothelial growth factor (VEGF), which instructs cells to grow and multiply and helps recruit new blood vessels to the tumor. They are testing several approaches that target various components of the tumor blood supply, namely one that deploys a decoy receptor capable of attracting and binding to all of the VEGF signaling molecules in the area and preventing new blood vessel growth. Moving beyond the microenvironment are research strategies that attempt to silence cancer-promoting genes and proteins deep inside the tumor rather than only on the cell surface. Investigators are pioneering siRNA technology, which uses short fragments of RNA to block gene activation. These fragments are wrapped in a

liposome, or lipid particle, and delivered directly into the tumor. In preclinical studies, “we found that we could turn off proteins critical to tumor growth and decrease new blood vessel development,” Sood says. “The best effect was seen when combined with chemotherapy. We hope to see equally positive results in the clinic.” A burgeoning area of research is the growing association of chronic stress and ovarian cancer growth and progression. Studies have shown a connection between feelings of distress and the body’s inability to mount an immune response against cancer, but other biological factors had not been explored until recently. In a major breakthrough, investigators discovered that elevated levels of stress hormones activated a specific pathway responsible for the acceleration of tumor and new blood vessel growth. This pathway, they showed, could be blocked with a targeted drug and prevent future growth. “This discovery,” Sood says, “opens the possibility of interceding early in the treatment process with interventions that manage stress in these patients, which may affect the clinical course of the disease and ultimate outcome.” OUT OF THE LAB, INTO THE CLINIC While investigators know that a drug, or small molecule, that works well in culture or animal models may not always have the same response in humans, they are optimistic that what they bring forward to the clinic will translate into more effective therapies for women with ovarian cancer.

Anil Sood, M.D., and his colleagues are evaluating approaches that target various components of the tumor blood supply, namely one that deploys a decoy receptor capable of preventing new blood vessel growth.

A number of studies are evaluating agents that target both the tumor vasculature and defective genes and proteins thought to be responsible for the growth, proliferation and spread of ovarian cancer. The goal is to improve responses to frontline therapy, which initially are quite high, and to extend the amount of time patients have without disease. “Nearly 75 percent of women with advanced disease respond to several rounds of chemotherapy after undergoing surgery,” says Robert Coleman, M.D., professor in the Department of Gynecologic Oncology. “Unfortunately, for most of these women their disease comes back, requiring additional therapy that may or may not achieve a second remission because their tumor is no longer sensitive to the effects of chemotherapy.” Investigators are finding alternative ways to overcome chemoresistance, which is a key reason why many women with advanced disease don’t survive. Several genes have been identified either as being capable of pumping chemotherapy out of cells quicker or sequestering the drug into compartments within cells to circumvent its effects. Once these mechanisms are fully understood, drugs that selectively target these survival factors can be given to achieve greater success, according to Coleman. Still, the challenge continues to be how best to treat recurrent disease, or prevent it altogether. Investigators are mixing things up a bit to see if simply changing the dose and timing of chemotherapy may have an effect, or if adding a biologic or molecular-based agent to standard chemotherapy gives the desired outcome.

“We’re also looking at new ways to deliver chemotherapy,” Coleman says. “Traditionally, it’s been given intravenously, but research now shows that administering chemotherapy directly into the abdomen, or intraperitoneally, extends overall survival and may be most effective for women who have small-volume tumors limited to the abdomen.” With several novel drugs to choose from, investigators are on the verge of making substantial breakthroughs in the treatment of ovarian cancer and making a lasting difference in the lives of women affected by the disease. DETECTING EARLY DISEASE KEY TO SURVIVAL If detected early, ovarian cancer often can be managed and treated successfully. The survival rate among women diagnosed with early-stage disease, or when it’s still confined to the ovary, is 95 percent. That percentage dramatically decreases when the disease is found late, with less than 10 percent of women with stage IV disease surviving five years after diagnosis, according to Karen Lu, M.D., associate professor in the Department of Gynecologic Oncology. Thus, the development of a definitive screening test is of utmost importance. Capitalizing on advanced technology and the availability of ovarian tissue and blood samples stored in M. D. Anderson’s tumor bank, investigators are stepping up their efforts to identify markers that could detect early disease. CA125 is one marker under examination. While CA125 has been shown to be a useful marker to monitor women undergoing

O VA R I A N C A N C E R — A F O R C E T O B E R E C K O N E D W I T H

Investigators like Karen Lu, M.D., are stepping up their efforts to identify tumor markers believed to be elevated in ovarian tumors, which may signal early disease.

treatment for ovarian cancer, it can only identify 50 percent of stage I disease. Robert C. Bast Jr., vice president for translational research and developer of the CA125 blood test, is working with Lu in evaluating whether changes in levels of CA125 over time predict with higher probability the presence of early ovarian tumors when compared to a single value. Investigators realize that a panel of tumor markers, rather than one alone, may be necessary to accurately screen for the disease. They are actively pursuing many leads and testing the viability of several markers believed to be elevated in ovarian tumors. They hope one day to be able to offer a simple, inexpensive blood test. In the meantime, they are screening women who are considered to be at high risk either because of a strong family history of both ovarian and/or breast cancer or a known BRCA1 or BRCA2 gene alteration, and who wish to know whether they have a genetic predisposition for developing the disease. Simply having a family member with ovarian or breast cancer doesn’t mean a woman will get ovarian cancer, but it does place her at a higher risk than the general population, according to Lu. A woman who has an alteration in either the BRCA1 or BRCA2 gene, however, has up to a 40 percent lifetime risk of developing the disease. The likelihood of a woman of Ashkenazi Jewish ancestry developing the disease is even greater, as one in 40 of these women carry a BRCA alteration. “Identifying these women is critically important,” Lu says, “because a number of effective preventive measures can be taken to reduce their risk.”

AN OUNCE OF PREVENTION, A POUND OF CURE Currently, having a bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes) before any disease is detected offers the most dramatic effect, Lu notes. For premenopausal women who carry a BRCA1 or BRCA 2 gene alteration, prophylactic surgery can reduce their chance of getting ovarian cancer by greater than 95 percent and their risk of breast cancer by 50 percent. Although this procedure is highly effective in preventing ovarian cancer in high-risk women, it doesn’t offer complete protection because there is still a small chance of developing primary peritoneal cancer. This cancer affects the lining of the abdominal wall and has symptoms similar to ovarian cancer. Realizing surgery may not be a favored option for many women, especially those of childbearing age, investigators also are looking toward approaches to screening and prevention. As often as every six months, a woman at high risk is encouraged to undergo a pelvic and rectal exam; CA125 blood test; and a transvaginal ultrasound, a radiologic procedure that gives a picture of the ovaries and may detect cysts and small tumors. While there is no data indicating these tests can always pick up a tumor or reduce a woman’s risk of dying from ovarian cancer, they do offer a conservative way to monitor risk. Until more sophisticated screening tests come online and are sensitive enough to predict and detect early ovarian cancer in the general population, Lu says “bilateral salpingo-oophorectomy offers women the greatest protection against the disease.”

SYMPTOMS OF OVARIAN CANCER

varian cancer typically is not detected until its late stages because, when symptoms appear, they often are vague and mimic other more common ailments. Some symptoms that may suggest ovarian cancer include: Fimbria • Abdominal swelling and/or pain • Abnormal bleeding • Bloating and/or a feeling of fullness Uterus • Frequency and/or urgency of urination Cervix • Persistent gastrointestinal complaints such as gas, nausea and indigestion that can’t be explained by another cause • Change in bowel habits Anus • Unusual fatigue, backaches

Fallopian tube Ovary

Bladder

• Unexpected weight loss or gain

Urethra Vagina

If any of these symptoms lasts more than two to three weeks, women are advised to consult their physician.

Illustration by: Kathleen Wagner

A LEGACY OF TWO WOMEN LIFE LESSONS LEARNED While a diagnosis of ovarian cancer is hard to swallow and “very frightening,” as Buelow interjects, it has forever changed the way she, Rice and Podraza go about their lives. For them, it’s all about giving back, helping others and rethinking priorities. “It’s not stuff that is important,” Buelow says, “it’s people. You quickly learn that each day is a gift and that you don’t get to assume you’re going to have it, so any chance I get I try to be helpful, loving and kind.” In West Virginia, Rice is the talk of the town. Just one year after her diagnosis in 1998, she founded the National Ovarian Cancer Coalition’s West Virginia division. Rice says she’s all about educating women about ovarian cancer — arming them with information regarding symptoms and risk factors and, most importantly, encouraging them to listen to their bodies. “Women as caregivers are always worrying about their families and tend to put off their own health care,” Rice says. “We need to stop and take the time to go to the doctor when we have these subtle symptoms and take care of ourselves.” Podraza literally laces up her running shoes and takes her message to the streets, volunteering her time to help with M. D. Anderson’s Sprint for Life, an annual 5K fun run and walk. More than 2,000 women, men and children participate in this fundraising event to help bring more attention to ovarian cancer. Her outreach efforts extend beyond the run and into the clinic, where she supports others being treated for cancer and learns about “life through the people I meet. They come from all over the world and do all sorts of different things. I’m truly blessed to be part of their lives.” Three women, one mission — to help save lives.

The Blanton-Davis Ovarian Cancer Research Program at M. D. Anderson was created in 1996 to change the future for women with ovarian cancer. It was the nation’s first formal, comprehensive ovarian cancer research effort aimed at translating basic discoveries into improved therapies and management of the disease. The program is named after Laura Lee Scurlock Blanton and Sandra G. Davis. Mrs. Blanton lent her talents and support to the Ovarian Cancer Research Program as an advisor. She served as honorary chair for the program’s Sprint for Life 5K Fun Run & Walk and was a lifetime member of M. D. Anderson’s Board of Visitors. Mrs. Blanton led a valiant fight against ovarian cancer. She died in 1999 at the age of 71. Her husband, Jack S. Blanton, serves as an advisor to the Ovarian Cancer Research Program and is a member of M. D. Anderson’s Board of Visitors. Mrs. Davis battled ovarian cancer for four years. Her sweet nature and focused determination inspired her caregivers to accelerate efforts to improve the prevention, early detection and treatment of ovarian cancer. Mrs. Davis died in 1996 at the age of 49 and left two daughters, Kim and Wendy. Lee Davis, her husband, donated seed money for the creation of the Ovarian Cancer Research Program and serves as an advisor.

Bringing Tumors Into Sharper View by Eileen A. Ellig

Picture this: A day when physicians can detect the subtlest molecular changes within your DNA that may predispose to cancer not with a tissue biopsy or blood test, but with something much less invasive â&#x20AC;&#x201D; imaging. 10

“That’s the pie in the sky,” says Reginald Munden, M.D., D.M.D., chair ad interim of M. D. Anderson’s Department of Diagnostic Radiology. “Someday, we may be able to screen populations truly at risk for certain cancers and let them know if we see any early genetic transformations well before a tumor becomes visible or causes problems.” With new and improved imaging technology, the ability to do this may not be too far off. Advances in medical imaging, which initially was based solely on detection of anatomically different or abnormal structures, have made it possible to now visualize not only the body’s physiological function, but also various intracellular processes that promote cancer. When asked what is making so-called molecular imaging possible, M. D. Anderson radiologists point to “fusion imaging,” or the pairing of positron emission tomography with computed tomography. In diagnostic imaging, “I haven’t seen anything make that kind of an impact on the cancer patient since CT was introduced back in the 1970s,” says Donald Podoloff, M.D., head of the Division of Diagnostic Imaging and professor of nuclear medicine. When CT came on the scene, radiologists were able to understand each individual’s anatomy in greater detail than they were able to do with plain X-rays, bringing into three-dimensional view the body’s organs, bones and other tissues, as well as tumors. They now had a tool that could determine more precisely the location of a tumor in relation to critical structures and determine the stage of disease. PET emerged some 20 years later, providing a way to measure the metabolic, or chemical, activity of cells within the body — primarily the regional distribution of glucose, or sugar, in cancer cells. Tumors entrap and more readily absorb glucose than normal cells and show up as active bright spots on the PET scan, indicating their location and concentration throughout the affected organ, according to Podoloff. The latter is of particular benefit when it comes to identifying volumes of tissue within a mass that may be more or less sensitive to certain therapies. One drawback to using PET alone, however, is it doesn’t provide an anatomic landmark like CT. But add the two images together and “you now have a very powerful machine that can complete the picture,” Podoloff says. “It combines both form and function, and for addressing the cancer problem, this produces some unique opportunities because we know that the function of an organ is disturbed before its form.”

While viewing CT and PET scans separately offers benefit, combining the two technologies to produce one image gives Homer Macapinlac, M.D., a more complete picture of where a tumor is located, what structures are affected and whether a drug is reaching its target. Reginald Munden, M.D., D.M.D., foresees a day when imaging, instead of a biopsy or blood test, could be used to screen people at high risk for cancer and detect early genetic changes before a tumor becomes visible or causes problems. Partners in discovery “Frankly,” Munden says, “I don’t think any of us were truly aware of the benefit of merging PET with CT until we started looking at the images and saw the added sensitivity and specificity they provided in detecting and localizing tumors.” This technology, he adds, is contributing greatly to “our ability to characterize tumors and image the very biomarkers our clinical colleagues are trying to target.” There is a large body of research being conducted to develop molecular imaging agents that could trace whether a drug is actually reaching the tumor, being taken up in the cells and whether it’s working. “And we can do this not at a bench with a microscope — as is the traditional approach — but non-invasively in the context of the whole body and over time, which means repetitive imaging of these processes and close monitoring of therapies,” says Juri Gelovani, M.D., Ph.D., chair of the Department of Experimental Diagnostic Imaging. Use of the radiotracer fluorodeoxyglucose has proven beneficial in evaluating the early effects of Gleevec® in treating gastrointestinal stromal tumors, for example. Since these tumors take up a lot of sugar, they can easily be seen on a PET image, says Homer Macapinlac, M.D., chair of the Department of Nuclear Medicine and head of the PET imaging program at M. D. Anderson. Within 24-48 hours, he says, “we can determine if there has been a response even though the mass is still there. If it’s no longer absorbing glucose, for instance, then we know the

drug is working and that generally correlates with a good outcome. That’s the paradigm we hope to emulate for other novel therapies in the early assessment of treatment response.” A limiting factor, Macapinlac notes, is that while a good surrogate marker for active cancer, fluorodeoxyglucose doesn’t show proliferating cells or cell turnover, which might be a better index of tumor activity than glucose. To date, this is the only federally approved tracer for use in PET imaging. With Gelovani’s support, Macapinlac says, “we’ll soon have available to us tracers that are more specific in measuring these kinds of metabolic parameters.” On assignment Gelovani wants nothing less than to expose tumors, from the largest to the tiniest of metastatic cells that often go undetected until they have spread throughout the body. One way he and his team are doing this is by developing agents for molecular imaging with PET, MRI, single photon emission computed tomography and optical (near-infrared) imaging of tumor-specific receptor molecules and substrates to proteins that are critical in tumor cell signaling, metabolism and regulation of oncogene expression. They are investigating the potential use of several novel molecular imaging agents that can be used to predict or monitor the effectiveness of novel anti-cancer drugs that target specific proteins once they get inside the tumor and induce cell death or cut off the tumor’s blood vessel supply.

Juri Gelovani, M.D., Ph.D., and his colleagues are developing new molecular imaging agents and methods that will increase the sensitivity and accuracy of cancer diagnosis and treatment monitoring. With these imaging agents, they can bring tumors into view and then follow the drug and observe its activity in real time. This is highly important for clinicians “because previously the only method of validation was a biopsy-based assessment of gene expression from a single point in a tumor, which doesn’t describe heterogeneity either within the tumor or metastatic sites. It also doesn’t tell you what critical tumor genes had been activated, sustaining tumor survival and progression,” says Gelovani, who directs the Center for Advanced Biomedical Imaging Research. The center is one of six facilities that will comprise M. D. Anderson’s Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer. The team’s efforts to assist clinicians in finding better ways of targeting therapies doesn’t stop there. They also are employing cellular tracers that can be labeled with different imaging-sensitive reporter genes, such as herpes simplex viral thymidine kinase, or HSVTK, to track and assess the effectiveness of therapeutic cells in killing tumors. HSVTK, Gelovani says, is widely used as a pro-drug sensitization gene in combination with standard chemotherapies. Gelovani, who originally developed a technique to image this particular gene, says it also can be incorporated or co-expressed with other therapeutic genes, such as p53, in a variety of gene-delivery vectors. And if properly designed and expressed, he notes, HSVTK would provide a means of imaging and monitoring not only genetic therapies, but cellular ones as well.

In collaboration with Steven Kornblau, M.D., associate professor in the Department of Stem Cell Transplantation and Cellular Therapy, for example, Gelovani and his team have developed a tracer for monitoring transplantation of T cells genetically modified with HSVTK for treatment of leukemia. While these T cells are thought to elicit a graft-versus-leukemic response, they also can later cause graft-versus-host disease, a serious immune reaction of the donor’s cells to the recipient’s. “We’ll be able to image the location, migration and sitespecific proliferation of the T cells because all of the donor cells will have the reporter gene and we can inject our tracer multiple times to monitor the patient’s status and, hopefully, diagnose graft-versus-host disease before severe clinical symptoms develop. Until now, this could only be proven by a biopsy,” Gelovani explains. Armed with this early information, clinicians can then be proactive and administer drugs that can eliminate any diseased cells that may be present. Gelovani and his team also have joined forces with investigators from M. D. Anderson’s Departments of Cardiology and Stem Cell Transplantation and Cellular Therapy, and colleagues at Texas Heart Institute to develop a reporter gene system for monitoring the location, fusion and survival of stem cells injected into the myocardium, the thickest layer of the heart wall. “In a way, we’ll be able to visualize how many of those stem cells have developed into viable heart muscle,” Gelovani explains. “Using more conventional imaging approaches like

John Hazle, Ph.D. (back), chair of the Department of Imaging Physics, is collaborating with Jason Stafford, Ph.D.(right) and Kamran Ahrar, M.D., on the development of novel MRI techniques to monitor non-invasive or minimally invasive thermal therapies.

magnetic resonance imaging, we’ll also be able to determine how much of that newly formed myocardium has contributed to the function of the heart.” Similarly, the team is developing applications to image stem cells for cancer therapies. They have demonstrated, for instance, that genetically modified stem cells carrying the HSVTK reporter gene engraft into the supportive tissue (stroma) surrounding the tumor, even in microscopic cancer cells, and contribute to its growth. “Again with imaging,” Gelovani says, “we can better assess noninvasively how much of a drug (specifically, ganciclovir) is needed to induce tumor stromal collapse, based on the percentage of stem cells seen in the tumor.” With a dozen or so tracers under development, Gelovani is optimistic that new imaging agents will bring into sharper view various molecular abnormalities indicative of cancer and revolutionize the diagnosis and treatment of the disease. Phasing in “We’re beginning to transition into the clinical phase of evaluation with several of our tracer compounds,” Gelovani says, “which will initially focus on radiation dose absorption, biodistribution, metabolism and pharmacokinetics.” Next, his team will validate tumor activity by comparing the imaging results with a tissue biopsy, hoping to confirm that what they see on the image does in fact reflect the magnitude and duration of expression of the targeted gene or protein. Gelovani is quick to note that these early imaging studies are not intended to have any therapeutic effect, but are essential in establishing targeted tracers as a viable way for clinicians to understand early on what is happening at a molecular level in these tumors when a drug is given and to know whether it’s really affecting the target proteins. “The development of these imaging agents is imperative not only for monitoring therapies,” he says, “but also in ultimately helping to stratify patients towards therapies that will most likely be effective in their case — in other words to individualize therapies.” Macapinlac takes it a step further saying, “we also have an opportunity to let patients know within days rather than weeks or months whether their treatment is working. Having this information upfront provides patients with hope, the fervor to continue the treatment despite the side effects.”

The pairing of PET scans with CT scans is a tremendous advance in diagnostic imaging, according to Donald Podoloff, M.D., allowing radiologists to visualize various intracellular processes that promote cancer. 14

Marshall Hicks, M.D., and his team rely heavily on imaging technology to obtain biopsies and guide therapies.

Image-Guided Precision Donald Podoloff, M.D., head of M. D. Anderson’s Division of Diagnostic Imaging and professor of nuclear medicine, tells the story of his grandmother to illustrate how far imaging technology has come in diagnosing and treating cancer. “In 1955, my grandmother, who was then 60 years old, turned yellow over night. After a battery of tests, she underwent exploratory surgery, at which time her doctors found she was covered with cancer. “Today, a CT scan would have picked that up and she would have had a simple biliary drainage procedure (to relieve pressure in bile ducts caused by an obstruction) and the whole thing would have been done in a matter of hours not the seven to 10 days she spent in the hospital.” The exploratory laparotomy, which was a common operation 20 to 30 years ago, has virtually been replaced by CT or magnetic resonance imaging, Podoloff says, “because we can now look inside and see what’s going on without having to do surgery first.” Interventional radiologists at M. D. Anderson rely heavily on CT and MRI imaging to obtain biopsies and guide therapies, according to Marshall Hicks, M.D., professor of diagnostic radiology and head of interventional radiology. The generated images help them navigate during a procedure, allowing them to differentiate hard-to-see areas better and ensuring that they insert the needle in the right place.

Image-guided biopsies make up the bulk of the procedures. While most of these are done to determine stage of disease, Hicks and his team are increasingly being asked to sample various spots within a tumor to verify that an investigational drug is actually reaching its target and being expressed in the tissue. “The Food and Drug Administration is now saying that if you want to bring a new drug to market, we need to know where that drug goes, we need to see it and you need to prove the drug is there,” says Podoloff, noting that interventional radiologists are being besieged with questions that need answering. Beyond biopsies, interventional radiologists are performing procedures using imaging to block off the tumor’s blood supply, guide probes that can be heated or cooled to destroy tumors and to place infusion catheters into organs for drug delivery, among others. “The sophistication of the imaging is critical for what we do,” says Hicks, whose team is working collaboratively with colleagues throughout M. D. Anderson to develop novel and more sensitive image-guided drug and thermal delivery approaches, devices that can be used for diagnosis, palliation and treatment, and non-invasive ways to image tumor cell death. “We’re continually enhancing our techniques,” Hicks says, “so that we can shorten the time when newer applications can benefit our patients.”

C O M M E N TA R Y

Progress Against Cancer by Gabriel N. Hortobagyi, M.D.

The recent announcement that cancer death rates among Americans had dropped for the second consecutive year represents a positive trend. I’m especially encouraged because the continuing decline in cancer mortality has been achieved despite our growing and rapidly aging population.

Gabriel N. Hortobagyi, M.D.

As president of the 25,000-member American Society of Clinical Oncology, I’m often asked to assess progress against cancer. There are many factors responsible for the decreasing mortality, including earlier detection and improved therapies for multiple cancers plus the good news that we’re preventing more cancers caused by tobacco use, poor diet and excessive sun exposure. The thread throughout our progress is the payoff for the investment made in cancer research during the past 35 years. Those of us involved in translational research over this period have been confident that research would yield new knowledge to understand the molecular basis of cancer, treat it more effectively and eventually prevent many types of the disease. So I’m

heartened that we’re now realizing measurable results from the investment stimulated by the National Cancer Act of 1971. But I also want to emphasize that we need a strong new commitment and sustained funding to assure we’ll accelerate translating scientific discoveries into life-saving clinical applications. At the same time, we must act quickly to avert a serious crisis due to the predicted shortage of oncologists to treat many more Americans living long enough to develop cancer while caring for the steadily increasing number of cancer survivors. After a study commissioned by ASCO recently estimated a possible shortfall of at least 4,000 oncologists by the year 2020, I appointed a committee to recommend solutions.

On the positive side, a few weeks before the American Cancer Society announced the declining mortality rate, ASCO issued its annual report outlining major research advances in cancer treatment, prevention and screening. These six major advances were identified from a list of more than 30 notable achievements among 10 cancer types:

Herceptin.® An estimated 20 percent to 25 percent of patients have this aggressive, hard-to-treat breast cancer. • FDA approved dasatinib (Sprycel ) for chronic myelogenous leukemia

translational research led by

trial demonstrating that 92.5 percent

M. D. Anderson and other major

tolerate or had become resistant to imatinib (Gleevec®) had no evidence

to prevent human papillomavirus

of disease after taking dasatinib.

infection that causes cervical cancer, • Cetuximab (Erbitux®) became the

women worldwide each year. The

first FDA-approved new treatment for

U.S. Centers for Disease Control says

head and neck cancer in 45 years. A

more than 25 percent of American

large international study showed this

women are infected with this virus.

targeted therapy combined with highdose radiation slowed cancer growth

• Two targeted treatments for kidney

and prolonged survival in patients

cancer — the first in more than 20

with locally advanced head and neck

years — were shown to improve

cancer, thus providing better results

survival rates. The investigational

than radiation therapy alone.

drug temsirolimus (Torisel™) increased survival when given as a first-line

• A novel gene profiling test, called the

treatment for individuals with

lung metagene model, was developed

advanced, high-risk kidney cancer,

to predict which patients with early

while sunitinib (Sutent®) increased

stage non-small cell lung cancer

progression-free survival and response

would have disease recurrence and

rates when administered as a second-

should be treated most aggressively.

line therapy for advanced disease.

This accomplishment illustrates the increasingly important field

• The addition of lapatinib (Tykerb®)

of personalized medicine that uses

to chemotherapy produced bet-

genetic information to design tailored

ter control of cancer growth than

approaches to prevent and treat can-

chemotherapy alone for women

cer and other diseases.

with advanced HER2-positive breast cancer that had progressed after treatment with the targeted agent

result of many years of productive

patients following a phase I clinical

approved the first vaccine (Gardasil®)

which is diagnosed in almost 500,000

death rates and advances

cited in the ASCO report are the ™

of CML patients who could not • U.S. Food and Drug Administration

oth the declining cancer

institutions. While I’m pleased about these and other achievements on the immediate horizon, I’m also deeply concerned that we’ll lose our momentum unless the current yo-yo manner of supporting research is changed. Despite increases in the National Institutes of Health budgets, the fact is we’ve had a net decrease in overall research funds over the last few years. Right now, only one in every 10 highquality, peer-reviewed research grants is funded, producing a disastrous roller coaster for critical translational research, particularly for some of our brightest young scientists whose creative ideas can’t be pursued. ASCO will continue working diligently to raise awareness of the dire need for a stable and predictable form of federal funding. Our 2006 report proposes a minimum annual funding increase of 5 percent for future NIH budgets. Such a formula should be adequate to keep up with inflation and avoid losing any more ground, but higher increases will be needed to assure we can convert our emerging opportunities into tangible and practical applications for cancer diagnosis, treatment and prevention. Many people don’t realize that at least 75 percent of all cancers are diagnosed in individuals 55 and older and that this age group is growing faster than

C O M M E N TA R Y

any other. The report, forecasting a shortage of oncologists, notes the number of Americans diagnosed with cancer is expected to rise from 11.7 million in 2005 to 18.2 million in 2020. Simultaneously, the study predicts U.S. cancer survivors — now more than 10 million — will increase by 81 percent. This escalation can be attributed to treatment advances that are turning cancer into a chronic and controllable disease. As encouraging as this trend is, I’m worried we won’t have nearly enough oncologists to provide state-of-the-art therapies to so many new patients while properly caring for all of the survivors. That report showed more than one-half of the current 10,400 practicing oncologists are older than 50, meaning many of them will retire in the foreseeable future. Although about 500 new oncologists enter the field each year, there won’t be nearly enough to replace those retiring and meet the demands for increasingly complex care. In fact, we could face a shortage of 4,000 or more oncologists by 2020. The complete report will be presented at ASCO’s annual meeting in June, but I already have asked a group of academic training program directors and several leading oncologists to begin developing bold recommendations on what actions we should take concerning the projected shortage. Besides the lack of oncologists and the unreliable funding dilemma, another problem involves access to human biospecimens. These samples of tissues and blood taken from patients during surgeries, biopsies and routine tests are vital for scientists to study the molecular characteristics of cancer cells. Another recent ASCO report emphasized the need for specific guidelines to standardize biospecimen collection, storage and use, and called for creation of a national database to enable sharing information and expertise among researchers. Despite these deficits, I’m more excited than ever about the future of cancer research. At our annual meeting, we expect to hear hundreds of reports on promising translational research, including more effective targeted therapies for many cancers and difficult-to-treat subtypes. The investment in cancer research made over the past three decades definitely is paying off with the development of newer, smarter treatments and the initial steps toward personalized medicine. 18

The Man Behind the Commentary Patients throughout the world benefit from the pioneering contributions made by Gabriel N. Hortobagyi, M.D., to improve the outlook for breast cancer. His landmark translational research during the last three decades includes proving the effectiveness of preoperative chemotherapy to reduce the size of previously inoperable breast tumors so they could be removed and conducting numerous clinical trials that have led to better therapy for patients with all stages of breast cancer. Hortobagyi joined the M. D. Anderson faculty in 1976 following a two-year fellowship in medical oncology. He chairs the Department of Breast Medical Oncology, directs the Multidisciplinary Breast Cancer Research Program and holds the Nellie B. Connally Chair in Breast Cancer. He also is principal investigator on the Specialized Programs of Research Excellence grant for breast cancer. In June 2006, Hortobagyi began a one-year term as president of the American Society of Clinical Oncology. He is the first M. D. Anderson faculty member elected to head ASCO, the world’s leading professional organization representing physicians who treat people with cancer.

Melissa L. Bondy, Ph.D. by Mary Jane Schier

ecoming a detective wasn’t on her list of career choices

as a child growing up in Pennsylvania, but today Melissa L. Bondy, Ph.D., is widely admired as a modern Sherlock Holmes in the expanding field of epidemiology research. “I think being an epidemiologist is a lot like being a detective,” says Bondy, professor in the Department of Epidemiology at M. D. Anderson, “and I can’t imagine doing anything more fascinating or rewarding.” The age-old mystery that challenges her investigative instincts and organizational skills focuses on who develops cancer and why. Since joining the M. D. Anderson faculty in 1990, Bondy has conducted research aimed at understanding genetic susceptibility and other risk factors associated predominantly with brain tumors and breast cancer. She also has inspired two pioneering collaborative programs that combine the expertise from several other institutions. The first program is the Childhood Cancer Epidemiology and Prevention Center, a partnership formed in 2000 that links researchers at Houston’s M. D. Anderson, Baylor College of Medicine and Texas Children’s Hospital. Bondy, who is an associate professor of pediatrics at Baylor, directs the center. A few months ago, her vision for an international consortium was realized when the National Cancer Institute awarded M. D. Anderson an $11 million grant to lead the largest genetic study ever attempted on the causes and risk factors of primary adult and pediatric brain tumors known as gliomas. Bondy is principal investigator on the grant for the 15-institution consortium organized for the Gliogene study. “Primary brain tumors are relatively rare. Because so few researchers are studying brain tumor development, the collaboration of scientists from multiple institutions is very important ... and the progress we make working together can be translated into significant results much more rapidly,” Bondy explains.

A PIVOTAL DECISION Bondy’s desire to help make a difference in the global crusade against cancer evolved over more than a decade. After receiving her bachelor’s degree in psychology at The University of Texas at Austin, she saw the impact of poverty and lack of health care while volunteering for VISTA (Volunteers in Service to America). Then she did grassroots epidemiology as an intern on a project that confirmed aircraft mechanics had a higher incidence of brain tumors. That knowledge and a subsequent study in which she evaluated environmental exposures in an area with high brain tumor incidence led to her master’s in epidemiology from The University of Texas School of Public Health. Behind her red-rimmed glasses, Melissa L. Bondy, Ph.D., is uncovering the causes and risk factors associated with primary adult and pediatric brain tumors. 19

M e l i s s a L . B o n d y , P h . D.

Bondy believes that coming to M. D. Anderson in 1984 to work for Louise C. Strong, M.D., “was a pivotal decision.” Now a professor of clinical cancer genetics, Strong already was at the forefront of research involving generations of families with Li-Fraumeni syndrome, a rare condition in which members develop multiple primary tumors, including brain tumors, and early onset of cancer. “During the next few years, I identified about 250 children with brain tumors. That was meticulous detective work, going through tons of records and calling hundreds of relatives to get families’ medical backgrounds,” recalls Bondy, who used those findings to earn her Ph.D. in epidemiology from the UT School of Public Health in 1990. When she joined the M. D. Anderson faculty, Bondy began working with researchers who were analyzing genetic susceptibility and environmental determinants in breast, lung and colorectal cancers as well as brain tumors. Associates appreciated her tenacity in tackling tough projects and her infectious team spirit. She quickly became a major contributor to epidemiologic studies in the Rio Grande Valley, Egypt and the Middle East. Margaret R. Spitz, M.D., chair of M. D. Anderson’s Department of Epidemiology, says Bondy “constantly generates new ideas and approaches” that have resulted in accelerated genetic epidemiological research involving many institutions. In 2000, Bondy received a Faculty Scholar Award, and in 2001 she won the Julie and Ben Rogers Award for Excellence in Cancer Prevention. Both honors recognized her collaborative research, contributions as a mentor for a wide range of students and leadership in establishing the Childhood Cancer Epidemiology and Prevention Center. “By combining the research expertise of M. D. Anderson with Baylor and Texas Children’s, we can improve our understanding of the causes of childhood cancer, identify the best strategies for prevention and share this information with health care professionals around the world. The center’s goal is to apply what we learn through research to develop cancer screening and detection methods for children similar to those for many cancers that affect adults,” Bondy says.

AN IDEAL LEADER Bondy’s bridge-building skills convinced 15 centers in five countries to participate in her proposed international consortium to identify genetic predictors of primary brain tumors. At a time when so many research requests are approved but unfunded, NCI awarded an $11 million grant to M. D. Anderson to launch the historic collaboration. The Gliogene study aims to screen 15,000 individuals from at least 400 families who have had two biologically related members diagnosed with primary brain tumors. Study participants will provide their family

When Bondy isn’t working, she enjoys going for a walk with her 14-year-old twins Emily and Jacob, and their dog Jesse.

Bondy’s family is no stranger to cancer. She lost both parents to the disease and her grandmother Rose Glick (pictured) to a brain tumor. 20

medical history during either a personal or telephone interview and complete a risk questionnaire. Some individuals will be asked to provide blood samples that will help identify possible genes related to the development of gliomas. “By collecting family histories and blood samples, we’ll gain a better understanding of the hereditary factors of this rare disease,” Bondy says. In addition to the five-year NCI grant, the American Brain Tumor Association is supporting the genetic analysis of blood samples. This analysis for samples in the United States will be conducted by Ching C. Lau, M.D., Ph.D., associate professor of pediatrics and co-director of the Pediatric Oncology Program in the Dan L. Duncan Cancer Center at Baylor and director of the Cancer Genomics Laboratory at Texas Children’s Cancer Center. The analysis of other samples will be done at the Institute of Cancer Research in the United Kingdom. American centers joining M. D. Anderson and Baylor/Texas Children’s in the consortium include Brigham and Women’s Hospital, Case Western Reserve University, Columbia University, Duke University, Evanston Northwestern Healthcare, Memorial Sloan-Kettering Cancer Center, Mayo Clinic Rochester, University of California, San Francisco, and the University of Illinois at Chicago. Researchers from Gertner Institute in Israel, the Institute of Cancer Epidemiology in Denmark, the Institute of Cancer Research in the United Kingdom and Umea University Hospital in Sweden also are contributing. “Studying rare and highly fatal cancer sites is very difficult. Collaboration is the only fruitful way to see considerable progress in this field. We’ll continue to recruit other European centers to broaden the reach and impact of the Gliogene study,” notes Beatrice Malmer, M.D., Ph.D., associate professor at Umea University Hospital and coordinating principal investigator of the non-American collaborators. Bondy’s colleagues call her the ideal consortium leader. She was a founding member of the International Genetic Epidemiology Society and is nearing the end of a two-year term as president of the American Society for Preventive Oncology. She also is often asked to evaluate other institutions’ epidemiological research programs.

A SHARED COMMITMENT Like many people, Bondy has been motivated by losing family members to cancer. Her maternal grandmother died from a brain tumor, and both her parents died from other cancer types. “My fervent hope is that our collaborative efforts will pay off through better cancer prevention for future generations,” Bondy says. “I’m very lucky to be working with such a dedicated staff at M. D. Anderson and with so many other talented researchers who share this commitment.”

In collaboration with Bondy, Ching C. Lau, M.D., Ph.D., director of the Cancer Genomics Laboratory at Texas Children’s Hospital, will be analyzing blood samples collected for the Gliogene study.

BRIEFINGS CONQUEST SPRING 2007

Nigeria’s Letter of Intent

Partnering With Our Neighbor to the South A handshake and a signature were all that was needed to forge a new sister institution agreement with Mexico City’s Instituto Nacional de Cancerología. The partnership between M. D. Anderson and INCAN is based on their mutual commitment to research-driven patient care in a setting of academic excellence and represents a step forward in the global fight against cancer. As the leading institution and governing body for cancer policy, treatment, education and research in Mexico, INCAN shares M. D. Anderson’s strong interest in advancing programs in cancer prevention and translational medicine. Leaders and representatives from both institutions participated in a signing ceremony at INCAN that coincided with the 60th anniversary of its founding and a symposium on leukemia. They agree that leukemia, along with breast cancer and epidemiological studies, will be an initial area for collaboration. Specifically, investigators will further share population-based studies to understand the risk factors for development of certain cancers among Mexicans and Mexican-Americans, including M. D. Anderson’s Mexican-American Cohort Study — the largest study ever to focus entirely on the health needs of Mexican-American families. Additionally, the collaboration establishes a plan for a national Mexican tissue bank and faculty training and education activities related to breast cancer and leukemia, eventually expanding to include clinical research and translational projects. “For more than 30 years, INCAN has been a valuable partner to M. D. Anderson, and patients in Mexico and the United States have benefited from our shared knowledge,” says John Mendelsohn, M.D., president of M. D. Anderson. “This agreement formalizes a program to continue the important work we have accomplished together and advances our efforts to eradicate cancer throughout the world.” — Julie Penne

The 5,000-mile trip to Nigeria was one Lovell Jones, Ph.D., was happy to make. It marked a firstof-its-kind, trans-Atlantic effort to address cancer disparities among Nigerian and Nigerian-American populations. M. D. Anderson, the Health Disparities Education, Awareness, Research & Training Consortium and the Ministry of Health of the Federal Republic of Nigeria signed a Memorandum of Understanding, forming a partnership to collaborate on cancer research, education and training programs in Nigeria. The agreement was the result of the first cancer conference held in Abuja, Nigeria. A delegation from M. D. Anderson and other U.S. institutions joined with Nigeria’s medical community to discuss advances in cancer management, early detection and prevention of common cancers, and opportunities for creating public education and awareness-building campaigns. “The Nigerian government’s commitment to raising awareness of cancer and addressing cancer issues in West Africa is a critical cornerstone to begin unraveling cancer and other health-related disparities, particularly diseases affecting Nigerians and African-Americans who share the same genetic heritage,” says Jones, director of M. D. Anderson’s Center for Research on Minority Health and professor in the Department of Health Disparities Research. With a large percentage of African-Americans tracing their ancestry to Nigeria and surrounding West African nations, and Houston serving as home to the largest population of Nigerians in the United States, there is “a natural share and learn partnership between M. D. Anderson and Nigeria,” Jones adds.

Postdocs Speak Out What makes M. D. Anderson the best workplace in North America for new scientists? Collaboration, superior mentorship and research independence, according to The Scientist magazine’s fifth annual survey of postdoctoral research fellows. M. D. Anderson postdocs cited these qualities as the institution’s strong points, driving M. D. Anderson’s ranking from 29th in 2006 to first place in 2007. Fourth-year postdoctoral fellow Cara Benjamin, Ph.D., was not at all surprised with M. D. Anderson’s top billing. “This is a phenomenal institution with many opportunities to conduct important and independent research.” Benjamin, who earned her Ph.D. in veterinary anatomy at Texas A&M University, says she feels “extremely fortunate” to be working with Honnavara Ananthaswamy, Ph.D., professor in M. D. Anderson’s Department of Immunology, on research to understand the genetic mutations that cause melanoma. A postdoctoral appointment is the first step in a scientist’s career after earning a doctorate. Both a first research job and an extension of scientific education under the guidance of a senior scientist, it can be thought of as the scientific version of the residency undertaken by new physicians. “The Scientist makes the great effort to compile this survey each year, but the recognition really comes from our postdocs, and that makes this ranking most gratifying,” says Stephen Tomasovic, Ph.D., senior vice president for academic affairs and vice president for extramural programs ad interim at M. D. Anderson. “These results reflect the commitment of our research faculty and academic affairs departments to ensure postdocs have a full opportunity to advance research in their field while really learning the fine details of what it means to be a scientist.” The Scientist survey covered 11 categories, with postdoc respondents judging their institutions on such criteria as communication, mentoring, facilities, training, career preparation and compensation. The most important factor cited was the quality of training and career preparation offered by an institution.

Postdoctoral fellow Cara Benjamin, Ph.D., works alongside her mentor Honnavara Ananthaswamy, Ph.D., in unraveling the genetic causes of melanoma.

Moving Forward: Adolfo Sosa by Gail Goodwin

Adolfo Sosa is a kid magnet. All the pediatric patients at M. D. Anderson love his teasing manner and look up to him. He gets a kick out of them and says it hurts to know that they are dealing with cancer. Just a kid himself when he was diagnosed with leukemia, Sosa was at the start of his senior year in high school. His world of friends, classes and plans for college were put on hold. Actually, Sosa thought he had it pretty easy — his treatment was “no big deal” and was over quickly. He made the most of the activities arranged by the Department of Pediatrics, was featured in a Children’s Art Project catalog, finished high school at M. D. Anderson and went back to his hometown school to walk across the stage with his class. He made plans to start college in the fall. And then it started all over again. Sosa was back at M. D. Anderson in the fall of 2003 for a bone marrow transplant with his younger brother Alex, a perfect match, playing hero for him. Now, the cancer is gone, although Sosa continues to deal with some lingering side effects. A student at the University of HoustonDowntown, Sosa is studying business because “it offers lots of opportunity.” In his dreams, he’s the CEO of Pennzoil or maybe a sound engineer. In reality, he’s a student, a big brother, a little brother, a boyfriend, the praise and worship leader at his church and a sometimes sound technician for bands and other churches. His spiritual faith allows him to keep his positive attitude. “That’s all you’ve got — that good attitude,” Sosa says. “Never think too far ahead, take life a day at a time, move step by step and you’ll make it.”

THE UNIVERSITY OF TEXAS SYSTEM BOARD OF REGENTS

James R. Huffines, Austin Chair

Rita C. Clements, Dallas Vice Chair

Cyndi Taylor Krier, San Antonio Vice Chair

John W. Barnhill, Jr., Brenham H. Scott Caven, Jr., Houston Judith L. Craven, M.D., Houston

AFFILIATIONS

M. D. Anderson Cancer Center Orlando, Orlando, Florida M. D. Anderson Radiation Treatment Centers in Bellaire, Fort Bend, The Woodlands and the Bay Area Centro Oncológico M. D. Anderson International España, Madrid, Spain Christus Spohn Stem Cell Program affiliated with M. D. Anderson Cancer Center Outreach, Corpus Christi, Texas

Robert A. Estrada, Ft. Worth Colleen McHugh, Corpus Christi Robert B. Rowling, Dallas Randal Matthew Camarillo, Houston Student Regent

Francie A. Frederick Counsel and Secretary THE UNIVERSITY OF TEXAS SYSTEM ADMINISTRATION

Conquest is published quarterly by The University Cancer Foundation Board of Visitors on behalf of The University of Texas M. D. Anderson Cancer Center. All correspondence should be addressed to the Office of Public Affairs -Unit 229, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston TX 77030, 713-792-0658. E-mail: eellig@mdanderson.org. Articles and photos may be reprinted with permission.

Mark G. Yudof Chancellor

Kenneth I. Shine, M.D. Executive Vice Chancellor for Health Affairs THE UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER EXECUTIVE COMMITTEE

John Mendelsohn, M.D. President

Thomas W. Burke, M.D.

Stephen C. Stuyck, Vice President for Public Affairs David Berkowitz, Director of Publications and Creative Services Sandi Stromberg, Program Manager of External Publications Editor: Eileen A. Ellig Writers: Mary Jane Schier, Gail Goodwin, Scott Merville, Julie Penne Design: Michael Clarke Photography: Kevin McGowen, John Smallwood, F. Carter Smith, Mark Webb

Executive Vice President and Physician-in-Chief

Margaret L. Kripke, Ph.D. Executive Vice President and Chief Academic Officer

Leon J. Leach Executive Vice President THE UNIVERSITY CANCER FOUNDATION BOARD OF VISITORS OFFICERS

Marc J. Shapiro

For information on supporting programs at M. D. Anderson Cancer Center, please contact Patrick B. Mulvey, Vice President for Development, 713-792-3450, or log on to the Development Office Web site at www.mdanderson.org/gifts.

For information on patient services at M. D. Anderson, call askMDAnderson at 1-877-MDA-6789, or log on to www.mdanderson.org/ask

Chair

Peter R. Coneway Past Chair

Ernest H. Cockrell Chair-Elect

Nancy B. Loeffler

Vice Chair

C h e c k o u t t h e C o n q u e s t W e b s i t e a t w w w. m d a n d e r s o n . o r g / c o n q u e s t

Please check the appropriate box and return this page to the address above.

Please remove my name from the Conquest mailing list.

I received a duplicate copy. Please make the necessary correction.

Please change my name or address.

Address Service Requested

The University of Texas M. D. Anderson Cancer Center Texas Medical Center Public Affairsâ&#x20AC;&#x201D;229 1515 Holcombe Blvd. Houston, Texas 77030-4009

CONQUEST Nonprofit Org. U. S. Postage PAID Permit No. 7052 Houston, Texas