Pathways to Discovery - Fall 2018 - UChicago Medicine Comprehensive Cancer Center

Pathways TO DISCOVERY

AT T H E FO R E F R O N T O F C ANCE R CARE AND DIS COVE RY

Clinical Trials: Shaping Cancer’s Future FEATURE STORIES 1 MAKING PROGRESS AGAINST CANCER

THROUGH CLINICAL TRIALS 4 I N PURSUIT OF NEW AND BETTER TREATMENTS FOR CANCER

FALL 2018

Pathways TO DISCOVERY

AT THE FOREFRONT OF CANCER CARE AND D ISCOVERY

Fall 2018 E X E C U T I V E E D I TO R

Jane Kollmer SENIOR SCIENCE WRITER

Kathleen Goss, PhD E D I TO R I A L A DV I S O R S

Michelle Le Beau, PhD Marcy List, PhD P H O TO G R A P H Y

Chicago Tribune David Christopher Hilary Higgins Jean Lachat Megan Mekinda Michael Satalic Joe Sterbenc Nancy Wong Lisa F. Young DESIGN

Pivot Design, Inc. PRINTING

G Thomas Partners LLC Pathways to Discovery is a publication of the University of Chicago Medicine Comprehensive Cancer Center.

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From the Director Clinical trials enable researchers and clinicians to test promising new methods of addressing cancer, such as investigational new therapies or unique combinations of existing therapies, novel ways to diagnose cancer, or biomarkers to better predict a patient’s response to treatment.

At the University of Chicago Medicine Comprehensive Cancer Center, we offer a large portfolio of clinical trials that move the cancer field forward by improving the standard of care.

We are national leaders in clinical trials, and our experts often lead national initiatives with other institutions across the country to enroll patients.

This is especially important for trials involving rare cancers or personalized therapies.

Because clinical trials are such a critical part of making progress against cancer, we decided to dedicate this issue of Pathways to Discovery to them. In this issue, we take a look at everything involved in a clinical trial, from its conception and design all the way through to its enrolling of patients and follow-up. We also showcase a few innovative clinical trials being conducted at the Comprehensive Cancer Center that are boldly combining new technologies and techniques to move cancer forward.

In this issue, you will also find examples of our most recent research breakthroughs, new faculty, member honors, and other news and updates.

Thank you for your support, as always!

Michelle M. Le Beau, PhD Director, The University of Chicago Medicine Comprehensive Cancer Center; Arthur and Marian Edelstein Professor of Medicine

Against Cancer Clinical Trials MAKING PROGRESS

THROUGH

Clinical trials look at new ways to prevent, detect, or treat disease.

They are an integral part of all medical research, but especially for cancer, a complex group of diseases that require new and improved approaches for prevention, screening, diagnosis and treatment.

The medical community uses clinical trials to evaluate promising new methods of addressing cancer before they are made widely available.

There are many types of clinical trials, including those that evaluate approaches for cancer screening or prevention, or those that test new treatments or new combinations of treatments, called therapeutic trials. These structured studies are carefully designed to test the safety and effectiveness of new drugs, devices, vaccines, or ways of using known treatments.

“We continue to be much better equipped to deal with cancer thanks to what we’ve learned through clinical trials,” said Mark Ratain, MD, Leon O. Jacobson Professor of Medicine, associate director for clinical sciences at the UChicago Medicine Comprehensive Cancer Center. “Without this critical step, we would not be able to offer our patients new options that increase survival and improve their quality of life.”

LEADING UP TO A CLINICAL TRIAL Clinical trials can be thought of as the final step of a long process that begins with a scientific idea.

Before a new treatment can be used in humans, scientists spend years studying its effects on cancer

cells and in animals. Those data are published in peer-reviewed journals and contribute to the greater body of knowledge. These findings are the seeds of what may later lead to improvements in cancer treatment, prevention, diagnosis or detection.

“We continue to be much better equipped to deal with cancer thanks to what we’ve learned through clinical trials. Without this critical step, we would not be able to offer our patients new options that increase survival and improve their qualit y of life.”

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CLINICAL TRIAL PROTOCOLS Clinical trials involve very detailed and standard procedures for administering the new treatment or procedure and measuring its effects (both good and bad) on patients, compared to existing approaches. Clinical trials can originate from a physician at a medical center, from an industry group such as a pharmaceutical company, from the National Cancer Institute (NCI), or from a group or network of institutions working together across the country.

The process for conducting a clinical trial is highly structured. All clinical trials are led by a principal investigator, or the lead physician or scientist.

He or she creates a plan for the clinical trial known as a protocol. The protocol explains what will be done during the trial and all the details necessary to help doctors understand who should enroll.

Each trial is carefully designed to address how a particular cancer treatment will affect the people who choose to participate. At the University of Chicago Medicine Comprehensive Cancer Center, clinical trials are carefully examined by members of its Institutional Review Board, which focuses on patient safety, and its Protocol Review and Monitoring System, which focuses on the science by asking, for example, whether the study is designed well and if the results will reveal something important.

This rigorous review process is important for ensuring that a trial is conducted according to strict scientific and ethical principles, according to Marcy List, PhD, associate director for administration of the UChicago Medicine Comprehensive Cancer Center.

The Comprehensive Cancer Center’s Cancer Clinical Trials Office (CCTO) provides the infra­ structure to support successful clinical research across the University. The team is responsible for providing oversight and quality control for cancer clinical trials at the University of Chicago Medicine through centralized regulatory management, reporting, staff supervision and training, auditing, and event tracking.

Several federal government agencies also help ensure that all research is conducted with patient safety in mind. The NCI sponsors many of the cancer clinical trials going on at any one time and conducts its own review of these studies before they are approved. The final authority on clinical 2

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“The fact that every clinical trial must undergo review and approval from unbiased parties...ensures that the data obtained are high qualit y and that patients are not harmed.” trials is the Food and Drug Administration (FDA).

The FDA reviews clinical trial information and decides whether the results of a study indicate that the treatment is safe and effective enough to be approved as a standard treatment.

“Clinical trials are developed and run under the strictest standards,” said List. “The fact that every clinical trial must undergo review and approval from unbiased parties from beginning to end ensures that the data obtained are high quality and that patients are not harmed.”

Once approved, the trial is considered “active” or “open,” and is typically listed on searchable online databases, such as ClinicalTrials.gov or a cancer center’s website (e.g., https://cancer.uchicago.edu/ clinical-trials/) so that the principal investigator can begin to recruit patients. Because each clinical trial has different enrollment criteria, patients should work with their physician to find the best trial for them.

INFORMED CONSENT Clinical trials offer a chance to receive investiga­ tional medicines or procedures that experts hope might improve the treatment of cancer. This impor­ tant option is not limited to people who have run out of choices. In fact, there may be clinical trials for every stage of disease in dozens of cancer types.

Each person who enrolls in a clinical trial is informed about all aspects of a study’s treatments and tests, including why each portion of the study is necessary, as well as its possible benefits and risks, prior to deciding to participate. The principal investigator of a study is required to obtain the informed consent (generally written) from all

clinical trial participants prior to the start of the trial. During the informed consent process, the research staff will explain the details of the study to participants and respond to any questions and concerns.

Participating in a clinical trial is a decision that must be made by the patient, often with help from their family and doctor. It is important for patients to fully understand the potential benefits and risks of the trial.

Benefits may include access to new drugs and treatments before they are widely available, close monitoring of their healthcare and any side effects, the chance for them to play a more proactive role in their healthcare, and the opportunity to make a valuable contribution to cancer research.

Potential risks may include the possibility that the new drugs and procedures will have side effects that are unknown to clinicians and/or that the new treatments are less effective than current approaches.

Once a clinical trial enrolls the number of patients needed to complete the study, it becomes closed for enrollment. Participating patients are closely monitored and data are collected and recorded at certain intervals.

Any side effects reported by patients are noted.

After the study is completed, the sponsor or principal investigator may share the results by presenting at a national conference and/or by publishing in a scientific journal. Every clinical trial involves asking a key research question and by the end of the trial, the answer to that question should become clear. If the trial produces positive results, the new treatment can move on and either be tested further or implemented in routine medical practice.

Alicia’s Story

Breast and ovarian cancer are common in Alicia Cook’s family. Her grandmother, mother, sister, and aunt all had been diagnosed with breast or ovarian cancer. Most of them didn’t survive their cancer. That is why, when Alicia was diagnosed with triple-negative breast cancer (a type of aggressive breast cancer that is most common, and deadly, in AfricanAmerican women), she considered all of the options.

Alicia, her UChicago physician Olufunmilayo Olopade, MD, and the rest of her care team discussed whether a clinical trial was right for her. Ultimately, she chose to participate in a trial comparing treatment regimens for lymph-node-positive, high-risk women such as herself.

In this trial, patients were randomly assigned to one of three study arms. Alicia was assigned to the toughest arm where she received a total of 10 cycles of chemotherapy.

Although it wasn’t easy, Alicia believes this decision gave her the chance to access the best treatment and has led to her being a 15-year breast cancer survivor.

Alicia’s experience—and her family’s high risk of developing breast cancer because they carry a specific gene mutation—have motivated her to do more. She is an active and vocal breast cancer advocate and encourages cancer patients, especially African-American women, to consider participating in clinical trials.

“There is a lot of hard work that goes into clinical trials, but in the end it’s really all about helping patients,” said Amanda Spratt, technical director of the CCTO of the Comprehensive Cancer Center.

Additional Resources: National Cancer Institute, American Cancer Society

“...But, in the end it’s really all about helping the patients.”

Alicia Cook is a 15-year breast cancer survivor and advocate for participating in clinical trials.

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In Pursuit of New and Better Treatments for Cancer Basic and clinical scientists at the University of Chicago Medicine Comprehensive Cancer Center are working together to develop innovative therapies for cancer, helping healthcare professionals around the country—and around the world—treat cancer more effectively.

These trials also give our patients access to new treatments and therapies. Clinical trials are helping us make progress toward a cure.

As a NCI-designated Comprehensive Cancer Center and a lead site for the National Clinical Trials Network, we provide national leadership in developing clinical trials. We provide access to clinical trials to community oncologists and minority populations via a network of affiliated hospitals. Our robust portfolio of therapeutic clinical trials numbers more than 350, and we enroll approximately 1,000 patients each year.

For a full listing of available clinical trials, visit clinicaltrials.uccrc.org. Following are but a sample of clinical trials that are happening at the University of Chicago.

immunotherapy, not all patients respond to it and some may become resistant to its anti-cancer effect.

Therefore, many current clinical trials are focused on optimizing immunotherapy and identifying ways to predict response to these approaches.

Jason Luke, MD, assistant professor of medicine, and Steven Chmura, MD, PhD, professor of radiation oncology, recently led a phase I trial to test the safety of combining a specific immunotherapy with stereotactic body radiotherapy (SBRT) in patients with solid cancers that have spread to other parts of the body (metastasis). The immunotherapy used in this study was pembrolizumab,

Clinical trials are helping us make progress toward a cure.

Improving Outcomes with Immunotherapy Immunotherapy—an approach that mobilizes or harnesses a person’s immune system to treat cancer—has revolutionized how we treat many cancers, especially some traditionally hard-to-treat types of cancer. Despite the frequent success of 4

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a type of “checkpoint inhibitor” which releases the brakes on the immune system. SBRT precisely delivers high-dose radiation to a target tissue in a limited number of treatments, and has been shown to be effective for several types of early-stage and advanced cancer.

In this clinical trial, patients with solid cancers with at least two distinct metastases (sites of tumor spread)

received SBRT and at least one cycle of pembrolizumab. The combination therapy was generally well tolerated and safe, as similar rates of toxicity were observed with the combination as each treatment alone. Furthermore, the combination therapy showed promising clinical activity, and the percentage of patients whose cancer shrank or disappeared (called the overall response rate) was 13.2%.

Future studies are aimed at testing the immunotherapy/SBRT combination in larger, randomized studies and identifying biomarkers in the tumors that predict responsiveness to the combination.

(Luke et al., J Clin Oncol 36:1611-18, 2018)

A Treatment Option for Patients with Stage II Melanoma Immunotherapy has been a blockbuster success in advanced melanoma (stage III/IV) that has spread, or metastasized, quickly becoming the standard of care. However, in melanomas that are diagnosed at stage II, meaning they have not yet spread to the lymph nodes, there are limited treatments beyond initial surgery. These cancers have a surprisingly high risk of recurrence and historically poor survival. Melanoma is one of the few cancers that is increasing in incidence in the United States, and better treatments are needed for this aggressive skin cancer.

UChicago Medicine immunotherapy expert Jason Luke, MD, assistant professor of medicine, has led the development of a clinical trial to assess whether patients without lymph node involvement could be treated with a drug after surgery that activates their immune system to recognize and attack melanoma cells. Luke initially worked with a NCI-supported cooperative group to develop the study and the pharmaceutical company Merck is now sponsoring an international double-blind phase III study, called Keynote-716, to investigate whether or not the successful immunotherapy drug pembrolizumab (Keytruda) can work in patients with stage II melanoma after surgery.

Pembrolizumab has been associated with a 50% reduction in risk of recurrence in patients with stage III melanoma and extended survival for patients with metastatic disease, without the toxic side effects seen with chemotherapy. The Comprehensive Cancer Center was the first U.S. site to offer the trial, which is now enrolling patients at dozens of sites internationally.

Medical oncologist Jason Luke, MD, explains an immunotherapy clinical trial for advanced melanoma to a patient.

Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716), NCT03553836

A Novel Therapy for Advanced Blood Cancers A primary goal of many clinical trials is to test new promising drugs for the treatment of cancer. A collaborative phase I/II study led by Wendy Stock, MD, Anjuli Seth Nayak Professor in Leukemia, and Olatoyosi Odenike, MD, associate professor of medicine, with longtime collaborators in Japan, is testing the effectiveness of a new drug that targets a protein called MELK (for maternal embryonic leucine zipper kinase) in patients with blood cancer.

MELK is frequently overexpressed in a wide array of cancers, and high levels of its expression are associated with poor survival in patients with acute myeloid leukemia (AML) (Alachkar et al., Oncotarget 5:1237-82, 2014; Stefka et al., Blood Cancer J 6:e460, 2016). Based on compelling results from experiments in tumor cell lines and animal models showing that a MELK inhibitor has potent anti-tumor activity, this ongoing trial is studying the safety and potential response benefit of the drug in patients with refractory or relapsed AML (i.e., leukemia that does not respond to treatment or comes back), acute lymphoblastic leukemia, advanced myelodysplastic syndromes, advanced myeloproliferative neoplastic disorders, or advanced chronic myeloid leukemia.

‘De-Escalation’ Approach Reduces Therapy Side Effects in Head and Neck Cancer The standard treatment for head and neck cancers involves surgery followed by radiation, sometimes CANCER.UCHICAGO.EDU

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Tanguy Seiwert, MD, tests a new treatment approach for HPV-related head and neck cancers.

with chemotherapy, or chemotherapy and radiation therapy. This is called combined modality treatment. Such treatment invariably causes side effects and, often, in an effort to cure patients from their cancer, severe side effects occur, some acute (pain, radiation burn) and some long-term, including problems with speech, swallowing, tooth decay, dry mouth and diminished sense of taste.

Recent research advances have changed the paradigm for head and neck cancer treatment, based on the finding that head and neck cancers that are caused by certain strains of the human papillomavirus (HPV) have more favorable outcomes than those associated with tobacco and alcohol use and can be treated successfully with less intensive therapy.

Because HPV-related cancers respond well to therapy and are more easily cured, clinicians at UChicago Medicine are adjusting treatment with an approach called “de-escalation.” This involves identifying patients with HPV-related cancer and shrinking the tumor with a limited amount of chemotherapy, then treating them with surgery or 35 to 40 percent less radiation with smaller radiation fields.

This approach yields dramatically fewer acute and long-term side effects. Patients recover quickly, often within a few weeks. The de-escalation approach was confirmed by a clinical trial called OPTIMA and resulted in markedly improved outcomes and reduced toxicity. OPTIMA uses a risk-based treatment approach, giving 82% of patients de-escalated, and significantly less toxic treatment, while achieving a 95% cure rate—as good or better than national average with more intensive therapy.

A multidisciplinary team of experienced physicians in medical oncology, surgery, and radiation, including Tanguy Seiwert, MD, assistant professor of medicine, Nishant Agrawal, MD, professor of surgery, Alexander Pearson, MD, PhD, assistant professor of medicine, and Daniel Haraf, MD, 6

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professor of radiation and cellular oncology, are building off of the success of the recently completed OPTIMA study with a follow-up, second-generation clinical trial called OPTIMA II. In this study, patients will also be treated with new immunotherapy drugs, PD-1 inhibitors, to get their own immune system working to recognize and destroy cancer cells. The hope is to allow even more patients access to curative treatment, with significantly fewer side effects, a faster recovery, and a more personalized treatment approach, as opposed to the usual one-size-fits-all approach that is still common practice.

The research team is also now able to avoid radiation therapy altogether for some patients through transoral robotic surgery, a less invasive surgical approach that allows surgeons to reach tumors through the mouth and remove them safely, leading to fewer side effects and quicker recovery time. This approach essentially combines immunotherapy, chemotherapy, and surgery, but avoids radiation and is one arm of the ongoing OPTIMA II study. UChicago Medicine is the only center in Chicago and one of only a handful nationally and internationally offering de-escalation clinical trials.

Chemotherapy and Locoregional Therapy Trial (Surgery or Radiation) for Patients With Head and Neck Cancer (OPTIMA-II), NCT03107182

Leading the Field in Neuroblastoma Although fewer than 1 in 20 adults with cancer will take part in a clinical trial, the majority of children with cancer are enrolled on clinical trials.

Sequential randomized clinical trials conducted by pediatric cooperative groups during the past decades have led to a dramatic increase in survival rates for childhood cancer—nearly 70% over the past 40 years. Today, more than 80% of children with cancer survive five years or more. However, survival remains poor for subsets of pediatric cancer patients, including those with high-risk neuroblastoma, and better treatments are desperately needed.

Professor of pediatrics Susan Cohn, MD, is a leading authority on neuroblastoma, a cancer of peripheral nerve cells, and the most common type of cancer found in infants. Cohn is actively researching several aspects of neuroblastoma

and she played a leadership role in the design and development of several NCI-funded Children’s Oncology Group clinical trials for children with newly diagnosed neuroblastoma.

In addition, she is one of the few pediatric oncol­ ogists in the United States who is conducting phase I clinical trials of promising treatments for children who have relapsed neuroblastoma.

In April 2014, her team established the only 131 I-metaiodobenzylguanidine (MIBG) treatment program in Illinois at Comer Children’s Hospital.

This targeted radiotherapy has been shown to be one of the most active treatments for children with neuroblastoma that has not responded to standard therapy.

Now, through the Children’s Oncology Group, Cohn is recruiting patients for a randomized phase III clinical trial that will evaluate the efficacy of MIBG therapy in newly diagnosed children with high-risk neuroblastoma. Many drugs that are effective in the setting of relapse also lead to improved survival when they are integrated into treatment regimens for newly diagnosed patients.

If successful, this clinical trial will redefine the standard of care for children with neuroblastoma to include MIBG therapy.

NANT 2011- 01: Randomized Phase II Pick the Winner Study of 131I-MIBG, 131 I-MIBG With Vincristine and Irinotecan, or 131I-MIBG With Vorinostat for Resistant/ Relapsed Neuroblastoma, NCT02035137

Steven Chmura, MD, PhD, researches new ways to use radiation therapy to improve outcomes in cancer.

Personalized Screening vs. Annual Screening for Breast Cancer A decades-long debate has stymied the medical community about when and how often women should be screened for breast cancer. For the first time, a large-scale study is being conducted to clarify the safest and most effective guidelines for breast cancer screening.

The Women Informed to Screen Depending on Measures of Risk (WISDOM) Study will assess whether personalized screening is as safe, effective, and accepted compared to annual screening.

Academic medical centers in California and the Midwest, including the University of Chicago Medicine, starting in January 2019, are recruiting 100,000 healthy women to undergo one of two different approaches to breast cancer screening— annual mammography or a personalized, riskbased schedule. The personalized approach will consider multiple risk factors, including genetic markers, breast density, and family history, to determine how frequently someone should be screened. Over time, researchers can learn what risk factors are most important and adapt screening recommendations accordingly.

If the WISDOM Study is successful, women will gain a realistic understanding of their personal risk of breast cancer as well as strategies to reduce their risk, and fewer women will suffer from the anxiety of false positive mammograms and unnecessary biopsies. The investigators believe this study has the potential to transform breast cancer screening in the United States.

Enabling a Paradigm Shift: A Preference-Tolerant RCT of Personalized vs. Annual Screening for Breast Cancer (Wisdom Study), NCT NCT02620852

Charlie Betzold had a form of high-risk neuroblastoma and received MIBG therapy as part of a clinical trial. Today, the 5-year-old is healthy.

Comer Children’s Hospital is one of the few medical centers in the nation and the only one in Illinois to offer MIBG therapy.

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Research

Meet the Expert Walter Stadler, MD FRED C. BUFFETT PROFESSOR OF MEDICINE AND SURGERY

Walter Stadler, MD, is an expert in the treatment of prostate, kidney, bladder, and testicular cancers using the latest treatments for patients with locally advanced or metastatic disease. His research focuses on the development of new treatments for these urological cancers, including molecular and imaging markers for predicting response to various anti-cancer therapies. In addition to his clinical and research expertise, he holds various leadership positions, including chief of the Section of Hematology/Oncology and deputy director of the University of Chicago Medicine Comprehensive Cancer Center.

What is the most rewarding part of your job?

Having participated in and witnessed major changes and improvements in how we treat and care for cancer patients. The concept of chronic disease management and discussion of multiple options for care is something we could only dream about when I started my career. Going to clinic and seeing patients I first met more than a decade ago is not only a great joy, but justification for all our hard work.

What do you hope to accomplish during your career?

I want to continue to work on guiding institutions 8

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and individuals so that all our cancer patients, and not just a select few, have the opportunity for decades of life after a cancer diagnosis.

In what direction do you see cancer research in general, or your field specifically, going?

We are in the midst of a technological revolution that is and will be directly applicable to patients.

I believe that novel diagnostic and monitoring approaches will allow us to rapidly choose and modify therapies so that cancer can be controlled in the majority and cured in an increasing larger minority of patients.

Research

How did you get interested in studying cancer and/or treating cancer patients?

As long as I can remember, I was fascinated by the concept that normal, well-behaving cells could go rogue and do all this bad stuff. Understanding the how and why was always fascinating. Learning how rewarding it is to care for cancer patients in medical school sealed the deal.

Who inspires you?

More people than I can count and thank. At the top of the list must be my parents and grandparents who came to this country with no education and no money, but supported and inspired me to work hard and pursue dreams; my patients who give me the motivation and reason for doing this work; and my wife and family who have allowed me to do this despite the disruptions to their own lives.

What is your favorite way to relax?

Many may know that my hobby is being a youth and high school soccer referee. I get to be with young people, maintain a connection to a game I love, get my exercise in a fun manner, and when people misbehave, I have two colored cards!

What is on your bucket list?

There are still multiple places I want to travel to.

Included on this non-exclusive list are Iceland, Costa Rica, Galapagos, Peru, Argentina, Thailand, and New Zealand.

What was the last book you read?

Calypso by David Sedaris. Wonderful author with poignant and humorous observations on life.

What do you love about Chicago?

Chicago is truly one of the great cities of the world, with a diversity of cultural, architectural, sporting, and dining opportunities that are truly second to none. From a professional perspective, having two major airports allows non-stop travel to almost anywhere in the world and makes Chicago a destination for multiple professional meetings, which helps limit time away from family.

Research Highlights Making Informed Decisions to Participate in Early-Phase Clinical Trials Phase I clinical trials are designed to test the safety of a promising new drug or device rather than to determine efficacy (i.e., how well they work). Patients with advanced cancer who are enrolled in these trials are often seeking clinical benefit and may not fully understand the primary goal of the study. Therefore, a multicenter team led by Christopher Daugherty, MD, professor of medicine, and including Mark Ratain, MD, Leon O. Jacobson Professor of Medicine, explored whether patients with advanced cancer have the cognitive ability to make informed decisions to participate in phase I clinical trials. Of the 118 patients evaluated, fewer than half recalled the purpose of the trial, as disclosed by the physician. Patients older than 60 years of age, in particular, were less likely to recall the trial purpose and had deficits in memory, attention and executive function (the set of skills that help plan, organize and complete tasks). Together, these findings suggest that cognitive function should be considered when enrolling advanced cancer patients into phase I trials, and that clinical and communication support tools or interventions should be developed and utilized to assist these patients with decision-making.

Hlubocky et al., J Clin Oncol 36:2483-91, 2018

What could you do without?

The segregation and concentration of socioeconomically depressed neighborhoods in certain parts of the city is certainly something that needs to improve and change.

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Research

Research Highlights (continued) Inherited Mutations in Malignant Mesothelioma

Endometrial cancer cells

New RNA Modification Critical for Endometrial Cancer When the laboratory of Chuan He, PhD, John T. Wilson Distinguished Service Professor of Chemistry, discovered a new type of reversible tag or modification on messenger RNA, called N6-methyladenosine (m6A) methylation, it was unclear whether it played a role in cancer. In a transdisciplinary collaboration with Ernst Lengyel, MD, PhD, Arthur L. and Lee G. Herbst Professor and Chair of Obstetrics/Gynecology, He and his team found that human endometrial cancers frequently have mutations in a gene encoding a key component of the “writer� machinery that puts on the RNA tag (a gene called METTL14), and 70% of endometrial tumors have reduced levels of m6A methylation. In functional studies, they showed that loss of METTL14 and reduced m6A methylation promotes endometrial cell proliferation and tumor growth in cell lines and animal models.

The investigators also identified the molecular events that mediate the effect of m6A methylation, namely regulation of AKT activity, which is critical for discovering potential therapeutic targets to be tested in future studies.

Liu et al., Nature Cell Biol 20:1074-83, 2018

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Malignant mesothelioma is an aggressive cancer that develops in the lining of the chest (pleura) and abdomen (peritoneum). Although mesothelioma is strongly associated with asbestos exposure, some patients have little or no history of exposure, suggesting that some individuals may have an underlying inherited susceptibility to develop the disease. Jane Churpek, MD, assistant professor of medicine, led an international team with additional Comprehensive Cancer Center faculty, Hedy Kindler, MD, professor of medicine, Kiran Turaga, MD, associate professor of surgery, Dezheng Huo, MD, PhD, associate professor of public health sciences, Zejuan Li, MD, PhD, formerly an assistant professor of human genetics, and Jeremy Segal, MD, PhD, assistant professor of pathology, to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma. The team identified 24 germline mutations in 13 genes in 23 (12%) of 198 patients, the most frequent of which were in the BAP1 gene. Many of the patients carrying these inherited mutations in cancer susceptibility genes were those with peritoneal malignant mesothelioma, minimal asbestos exposure, young age, and a second cancer diagnosis. Importantly, many of the genes encode components of DNA repair and homologous recombination pathways, providing rationale for studying these pathways in mesothelioma.

Panou et al., J Clin Oncol 2018 Aug 18 Epub ahead of print

A mesothelioma cell

News

NOVEL ROBOTIC DEVICE ALLOWS BETTER DIAGNOSIS OF LUNG CANCER

The robotic device is operated by a controller to guide the scope deep into the lung.

To diagnose lung cancer, physicians rely on advanced bronchoscopy, a minimally invasive procedure that lets them see inside a person’s airways with the help of a small camera (or scope) attached to a long tube that’s inserted through the mouth. But the technology has limitations in how far it can reach. D. Kyle Hogarth, MD, FCCP, associate professor of medicine, helped the company Auris Health create a robotic device that would attempt to remedy scoping’s existing limitations and get physicians farther into the body with greater precision and accuracy. Called the Monarch Platform, the device was cleared by the U.S. Food and Drug Administration for robotic bronchoscopy in March 2018. Three months later, UChicago Medicine became the second hospital in the nation—and the first in the Midwest—to begin using the novel platform. Hogarth says the tool enables access to the far reaches of the lung for more accurate diagnoses.

At the Forefront of Minimally Invasive Robotic Surgery The UChicago Medicine robotic surgery team hit a milestone in August when they treated their 10,000th patient. Robotic surgery enhances a surgeon’s precision, resulting in faster recovery times and shorter hospital stays. UChicago Medicine is one of the only hospitals in the country to provide a wide variety of robotic surgical procedures.

Yoga Event Celebrates Wellness for Breast Cancer Patients In late September, UChicago Medicine held a free wellness event to kick off breast cancer awareness month. Participants from the community were able to take advantage of free mammograms, Zumba dancing, and yoga therapy, as well as prizes, giveaways, and crafts.

Certified yoga therapist Raquel Jex Forsgren leads a class in yoga poses.

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News

New Faculty For more information about our new faculty, visit uchospitals.edu/physicians.

UChicago Medicine Nationally Ranked for Cancer by U.S. News For another year, U.S. News & World Report named UChicago Medicine as one of the best hospitals in the country. Cancer was one of the seven adult specialties that were recognized and UChicago Medicine also received a “high-performing” ranking in five procedures and conditions, among them colon cancer surgery and lung cancer surgery.

Jessica Donington, MD, professor of surgery and chief of thoracic surgery, is an expert thoracic surgeon who specializes in lung cancer and treats people at all stages, providing a personalized approach to diagnosis and treatment using the latest technology and innovations, including minimally invasive and robotic surgery.

OIiver Eng, MD, assistant professor of surgery, focuses on the treatment of cancers in the abdomen and, in particular, cancers that have spread to the peritoneum, the membrane that lines the abdominal cavity. He specializes in complex cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) for locally advanced and metastatic cancers which have disseminated in the abdomen.

PIPELINE PROGRAMS INTRODUCE STUDENTS TO CANCER RESEARCH

Northside College Prep High School teacher Lidia Ortiz presents a poster of her work with Lucy Godley, MD, PhD, to Senator Dick Durbin.

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In August, Senator Dick Durbin (D-Ill.) visited the UChicago campus to hear from young people who participated in UChicago Medicine Comprehensive Cancer Center’s summer research programs. That day, the more than 30 high school and undergraduate students and educators who participated in ResearcHStart and National Cancer Institute-sponsored Chicago EYES on Cancer pipeline programs summarized the research they worked on over the summer through poster and oral presentations.

News

Cancer Can’t Compete Campaign Raises Money for Research, Patients, and Families

Faculty Awards and Honors

Maryellen Giger, PhD, A.N. Pritzker Professor of Radiology, and Gregory Karczmar, PhD, professor of radiology, were selected as inaugural fellows for the Society of Breast Magnetic Resonance Imaging (MRI). Giger is also the recipient of this year’s Illinois Biotechnology Innovation Organization’s iCON Innovator Award.

Anthony Rizzo

The University of Chicago Medicine has partnered with World Champion first baseman Anthony Rizzo, the Anthony Rizzo Family Foundation, Mariano’s and the Chicago Tribune in a campaign to raise money for cancer research and support for children and families who are fighting the disease. Proceeds from the multifaceted campaign, called Cancer Can’t Compete, will be split evenly between the UChicago Medicine Comprehensive Cancer Center and the Rizzo Family Foundation.

For sixteen weeks leading up to the World Series, the Chicago Tribune included weekly advertisements highlighting UChicago Medicine’s work and spreading awareness of the campaign. In addition, Mariano’s shoppers had the opportunity to contribute in-store donations. Visit uchicagomedicine.org/ cancercantcompete to learn more.

Olufunmilayo Olopade, MD, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, Associate Dean for Global Health, and Director of the Center for Clinical Cancer Genetics, is one of six Illinoisans who will receive the 2019 Order of Lincoln, the state’s highest honor for professional accomplishments and public service.

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