Emory Winship Cancer Institute Magazine Fall 2019

FALL 2019

CHARTING A NEW FUTURE FOR LUNG CANCER PATIENTS LIKE BRANDI (p. 6)

In si d e : TARGETING METABO L I SM

p.14

THE N URSES W HO GI VE HOP E

p. 1 6

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“This work has direct implications for our patients, both in terms of quality of life and longevity.”

–Taofeek Owonikoko,

lung cancer physician scientist

6

6 On the cover: Brandi Baker (on the cover with daughter Karsyn and left with daughter Gabrielle) leads an active life with family and career. Last year, a stage IV lung cancer diagnosis threatened all that. Now, she’s doing well on a targeted therapy but the clock is ticking. Her story and how Winship is working to transform the future for lung cancer patients like her. Page 6

“In coaching, people don’t care about how much you know until they know about how much you care.”

–Nicki Collen, head coach of the WNBA’s Atlanta Dream women’s basketball team and Winship 5K Grand Marshal

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3 15

14 Winship Magazine | Fall 2019 From the Executive Director 2

The Winship Win the Fight 5K 22

Winship’s leadership role in advancing

Targeting metastasis through metabolism 14

cancer research.

Could a common antiseptic help reign

spirit and true grit.

In the News 3

in cancer metastasis?

The cancer community shows its team

Point of View

The Emory Proton Therapy Center treats

“Can you help me live?” 16

Mapping a calmer passage 24

its 100th patient; Winship welcomes new

A photo essay pays tribute to the people

A melanoma surgeon guides his patient

leaders in radiation oncology and nursing;

who deliver hope and loving care.

through treatment.

new research funds for cellular therapy.

Features

24

Giving Back

Gaining ground on lung cancer 6

Coach Nicki Collen leads the Winship 5K 21

Winship investigators are working to

Losing a loved one to cancer inspired

advance the most promising treatments

Coach Nicki to be the 5K Grand Marshal.

Cancer tested my ability to trust.

for patients with lung cancer.

Emory | Winship Magazine is published biannually by the communications office of Winship Cancer Institute, a part of the Woodruff Health Sciences Center of Emory University, emoryhealthsciences.org. Articles may be reprinted in full or in part if source is acknowledged. If you have story ideas or feedback, please contact catherine.s.williams@emory.edu. © Emory University 19-WINSHIP-0522

Emory University is an equal opportunity/equal access/affirmative action employer fully committed to achieving a diverse workforce and complies with all federal and Georgia state laws, regulations, and executive orders regarding nondiscrimination and affirmative action. Emory University does not discriminate on the basis of race, age, color, religion, national origin or ancestry, sex, gender, disability, veteran status, genetic information, sexual orientation, or gender identity or expression.

Website: winshipcancer.emory.edu. To view past magazine issues, go to winshipcancer.emory.edu/magazine.

Editor: Catherine S. Williams Art Director: Stanis Kodman

Photographer: Jack Kearse Production: Carol Pinto

Winship | From the Executive Director

NEW PATIENTS SEEN PER YEAR:

NUMBER OF CLINICAL TRIALS:

NUMBER OF WINSHIP MEMBERS:

2009: > 5,000 2019: >17,000

2009: >150 2019: >275

2009: >260 2019: >500

For more statistics, see the Winship By The Numbers insert in this issue.

SEPTEMBER MARKED MY 10TH ANNIVERSARY AS EXECUTIVE DIRECTOR OF WINSHIP. Winship had just

PHOTO BY ANN WATSON

received its first designation from the National Cancer Institute (NCI) in 2009 when I took the helm. Since then, Winship set its sights on attaining the NCI’s highest designation. In 2017 we did it, becoming Georgia’s first and only NCI-designated comprehensive cancer center.

Looking back over the last 10 years, what strikes me is not just how far Winship has come, but how far cancer research itself has come. We’ve gained tremendous knowledge and momentum from discoveries that are changing the way cancer is prevented, detected, and treated.

Lung cancer is a perfect example. Ten years ago, there were few effective treatment options for patients with advanced lung cancer. A stage IV lung cancer diagnosis often meant a poor quality of life over a severely limited life span. But in the past ten years, two research developments—immunotherapy and targeted therapy—have led to treatments that help lung cancer patients live years longer with better quality of life.

Winship investigators have been at the forefront of both developments.

In 2009, Winship physicians were among the first to analyze lung cancers with molecular panels that identify specific genetic mutations. Today, many Winship lung cancer patients are effectively treated with drugs that target their particular genetic

We’ve gained tremendous knowledge and momentum from discoveries that are changing the way cancer is prevented, detected, and treated.

[ Winship Magazine

mutation. The other area that has changed lung cancer treatment is the development of immunotherapy drugs, including those known as checkpoint inhibitors. Now, Winship investigators take on the challenge of making these therapies even more effective.

This year, the NCI awarded a $9.7 million Lung Cancer SPORE (Specialized Program of Research Excellence) grant to Winship, with the goal of improving outcomes of lung cancer patients by addressing current challenges, such as drug resistance, and by developing the next generation of therapeutic strategies. This grant reflects Winship’s nexus of top lung cancer researchers in basic science, translational research, and clinical research, but it also supports our strength in creating teams of researchers from areas outside of lung cancer, teams who will spark new ways of thinking about this cancer and develop fresh approaches to it. The SPORE team is made up of researchers from many disciplines at Emory—biostatistics, pathology, immunology, drug development, surgery, genetics, and more.

We’ve grown in other areas as well. Today, Winship treats patients with proton therapy—a technology that was just getting off the ground in 2009—at our new facility in midtown Atlanta, and we’re pursuing practice-changing technologies such as re-engineering immune cells.

Our way of looking at cancer has evolved over a long period of time, but never more dramatically than in the past decade. We see each person’s disease as unique, demanding a highly personalized and specific strategy with many tools and approaches. Winship is a vital force and leader in this exciting and rapidly changing world. w

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Wally Curran

]

Winship | In the News

one of the

milestone of having treated more than 100 patients at the Emory Proton Therapy Center since opening in December 2018.

PHOTOS BY ANN WATSON

100

This summer, Winship Cancer Institute celebrated the

S

tephen Brinkman was one of those 100 patients and a good example of why proton therapy is such a valuable tool in treating patients with certain kinds of cancer.

Brinkman, a 36-year-old Methodist pastor from Columbus, Georgia, was diagnosed with a low-grade glioma, a type of brain tumor. It was surgically removed in 2010 but when it recurred this year, Brinkman’s surgeon referred him to Winship radiation oncologist Jim Zhong.

Proton therapy delivers a high dose of radiation to a tumor with less radiation exposure to healthy tissues. After his first visit with Zhong, Brinkman says he “left with hope that something could be done.”

“Mr. Brinkman’s tumor is located in a section of the brain next to some very important areas—the temporal lobe, the hippocampus, and the pituitary gland. Those areas are used for memory creation, for speech, and for making hormones,” says Zhong. “With X-ray radiation, those areas would get a significant dose of radiation, but using proton we’re able to shape the beam to avoid treating those areas and avoid the side effects.” [ Winship Magazine

Stephen Brinkman rang the bell signaling the end of proton therapy. His wife Emily, daughters Emma Kate and Zoe, parents Kathy and Mark Brinkman, oncologist Jim Zhong, and radiation therapists Anh Duong and Julia Novotny.

Brinkman traveled back and forth for six weeks to the proton center in midtown Atlanta from his home in Columbus, where he and his wife are raising four children. Although it was a lot of round trip driving, he was determined to get home and be with his family every day.

Brinkman is no stranger to the Atlanta area, having attended Emory’s Candler School of Theology for his master’s of divinity and the Columbia Seminary in Decatur for his doctorate.

During daily treatments, Brinkman says he didn’t feel anything physically, but he spent his time in prayer. “God, here I am. You’ve done incredible things through medical technology and doctors and research. I’m grateful for the opportunity to have it and then just trusting….whatever it can’t do, you do.”

Brinkman finished proton therapy on July 15 and is continuing with chemotherapy. He’s feeling well, loving life, and keeping long-term goals in mind. “I look forward to raising our children, being a pastor, maybe one day doing weddings for my kids, all those things I hold tight to.” w

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Winship | In the News

Pioneering new radiation treatment options of his 21-year medical career invested in discovering new radiation treatment options for cancer patients. When he arrived at Winship Cancer Institute in September from Washington University’s Siteman Cancer Center, he brought with him a wealth of bench-to-bedside experience and enthusiasm for advancing research in new technologies, including proton therapy.

As the new executive vice chair of Winship’s Department of

patients at the Emory Proton Therapy Center in midtown Atlanta.

He is also the newest team member of the National Cancer Institute Lung Cancer SPORE grant (see story, page 6) at Winship.

“Winship is doing an amazing job pioneering research in innovative radiation treatment options for patients,” says Bradley. “In my role as the executive vice chairman, I plan to enhance our research infrastructure so we can have a stronger impact on the field of radiation oncology and most importantly, in our patients’ lives.”

Bradley is eager to launch clinical trials for proton patients and those who receive flash radiation therapy, an emerging treatment that minimizes side effects such as brain damage

Radiation Oncology, Bradley plays a key role in treating lung cancer

and lung fibrosis. w

PHOTO BY STEPHEN NOWLAND

JEFFREY BRADLEY has spent much

Curran receives Gold Medal THE AMERICAN SOCIETY FOR RADIATION ONCOLOGY (ASTRO) AWARDED ITS HIGHEST

award. This award also recognizes my outstanding colleagues in cancer research

HONOR, THE GOLD MEDAL, TO WINSHIP EXECUTIVE DIRECTOR WALTER J. CURRAN, JR.

during the 2019 annual ASTRO meeting in September. The Gold Medal is given to revered ASTRO members who have made outstanding contributions to the field of radiation oncology in research, clinical care, teaching, and service.

“ASTRO is an extraordinary organization, and I am deeply honored by this

ASTRO Board of Directors Chairman Paul Harari presents Wally Curran with the ASTRO Gold Medal.

and education in support of our patients,” said Curran.

Curran’s distinguished career was highlighted in a ceremony at ASTRO, including his leadership as group chairman and principal investigator of NRG Oncology, the largest of the five National Cancer Institute-funded cooperative groups. Curran also holds the Lawrence W. Davis Chair of Radiation Oncology and is chair of Emory’s Department of Radiation Oncology. w

New VP of cancer nursing WHEN LANA UHRIG BEGAN WORKING WITH ONCOLOGY PATIENTS 14

and be willing to change traditional paradigms to allow for more innovative and effective care delivery models.”

The commitment to world class research and innovation in patient care attracted Uhrig to Winship. “I look forward to collaborating with all the great talent at Winship.” w

YEARS AGO , she knew immediately these were the people she

wanted to serve. Uhrig, who joined Winship Cancer Institute this year as the new vice president of cancer nursing, brings experience in public health, basic and population science, and multi-disciplinary clinical care to her new role. She worked for 12 years practicing hospital medicine in a cardiac step-down unit before shifting her focus to oncology nursing.

“My personal experiences with cancer shape my perspective on how we screen, diagnose, and care for our patients,” says Uhrig. “We owe it to our patients to deliver exceptional service [ Winship Magazine

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]

Winship | In the News

WINSHIP ADVANCES CANCER CELLULAR THERAPY HARNESSING THE BODY’S OWN IMMUNE SYSTEM IS ONE OF THE MOST PROMISING APPROACHES TO CANCER TREATMENT. Our immune

systems are meant to recognize and destroy invading pathogens, but our immune cells often don’t have what they KE

need to carry out that function

ITH CH

Winship Cancer Institute is among a handful of cancer centers in the United States to receive this award.

Madhav Dhodapkar, director of the Winship Center for Cancer Immunology, will serve as project leader. Co-investigators include Max Cooper, professor in the Department of Pathology and Laboratory Medicine and the Emory Vaccine Center, and Krishnendu Roy, director of the Center for ImmunoEngineering at Georgia Tech.

Dhodapkar says “The collaborative effort between Winship and Georgia Tech will focus on three unmet needs to improve cell therapy of myeloma: new platforms for antigen targeting, preclinical humanized modeling of cell therapy, and scalable manufacturing.”

The goal of Winship and Georgia Tech investigators is to use the supplemental funding from the NCI to initiate Phase I clinical trials, which are the first phase for testing new therapies in humans. To support those efforts, a new cellular therapy lab will be opening soon in the Emory University Hospital Tower. w AM

BE

with cancer cells.

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PH

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IB OL

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PHOTO BY BILLY HOWARD

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Now, Winship Cancer Institute has a grant to advance research in cancer immunotherapies and move them quickly from the laboratory into clinical trials and approved treatments. The award, a supplement to Winship’s National Cancer Institute (NCI) Cancer Center Support grant, will enable researchers at Winship and Georgia Institute of Technology to create interdisciplinary teams of translational cancer immunologists, basic immunologists, and biomedical engineers who will work together to improve cell therapy for patients with multiple myeloma, a hematologic malignancy characterized by the growth of clonal plasma cells in bone marrow.

One focus will be on chimeric antigen receptor T-cell (CAR T-cell) therapies. Currently, CAR T-cell therapies are approved by the Food and Drug Administration for patients with certain types of leukemia and non-Hodgkin lymphoma but are only available for myeloma patients in clinical trials.

Madhav Dhodapkar is leading Winship’s work in advancing cellular therapies.

[ Winship Magazine

| 5 | Fall 2019

]

GAINING GROUND ON IT STARTED WITH A COUGH. Just a small cough, nothing painful and certainly nothing Brandi Bryant had any time to worry about.

A mother of four young children with a career as a publication coordinator, Bryant led a full, active life. In the little time she had to herself, she kept fit, sometimes walking as much as 30 miles a week. She had never smoked.

[ Winship Magazine

| 6 | winshipcancer.emory.edu

]

LUNG CANCER But the cough turned into shortness of breath. Soon after, Bryant, then 39 years old, received a diagnosis of stage III nonsmall cell lung cancer (NSCLC), the most common type of lung cancer.

“I break down in the office,” she wrote on her blog, recalling her thoughts in that life-changing moment. “I am the one

who takes care of EVERYTHING in my house…I CANNOT be sick.”

Lung cancer has long been difficult to treat. Most cases are diagnosed at an advanced stage, and a decade ago, few options were available besides radiation and chemotherapy, with modest effectiveness. That is starting to change. Recent

[ Winship Magazine

| 7 | Fall 2019

]

by QUINN EASTMAN

years have seen the advent of immunotherapy, in which the patient’s immune system is re-activated to attack the disease, and targeted therapies, chosen according to the genetic makeup of a patient’s tumors.

These treatments are capable of beating back even advanced cancers, making them appear to vanish from the body. Yet they

Leaders of Winship’s Lung Cancer SPORE (left to right): Rebecca Pentz, Zhengjia Chen, Dongkyoo Park, Suresh Ramalingam, Xingming Deng, Haian Fu, Gabriel Sica.

“We want to develop personalized immunotherapy and targeted therapy options.”

Suresh Ramalingam Winship Deputy Director Lung Cancer SPORE grant co-leader

have their limitations. Immunotherapy drugs are only effective in about 20 percent of patients with lung cancer and can have severe side effects. Similarly, targeted therapies are relevant for just a fraction of lung cancers, and often stop working when the tumor cells they target become drug resistant.

At Winship Cancer Institute, lung cancer specialists think their field is at the beginning of a transformation. They want to make the benefits of the new treatments available to a larger number of patients.

“In the next few years, we plan to bring innovative approaches to improve the effectiveness of existing therapies for each lung cancer patient,” says Winship Deputy Director Suresh Ramalingam, co-leader of the Lung Cancer SPORE. “We want to develop personalized immunotherapy and targeted therapy options.”

With those goals in mind, the National Cancer Institute recently awarded Winship [ Winship Magazine

| 8 | winshipcancer.emory.edu

]

a five-year, $9.7 million Lung Cancer Specialized Program of Research Excellence (SPORE) grant, one of just four in the country. Winship’s Lung Cancer SPORE program includes three research projects, each aimed at strengthening a major tactic against lung cancer. It incorporates clinical trials examining immunotherapy and targeted therapy, and more basic research aimed at sensitizing cancer cells to radiation.

“This grant shows how we weave together basic science, translational, and clinical research, and it will spark new ways of thinking about the problems our patients face,” says Winship Executive Director Wally Curran.

The grant brings together experts not just in lung cancer, but in immunology, pharmacology, drug development, bioethics, and other areas. In addition, it is designed to nurture younger researchers, and allow them to test ideas that they haven’t had a chance to implement, says Haian Fu, leader of

Winship’s Discovery & Developmental Therapeutics Research Program and Ramalingam’s counterpart as co-leader of this SPORE grant.

“We bring new people into the field of lung cancer, and we also bring the cutting-edge research in other fields to bear on lung cancer,” Fu says.

When she began her treatment journey in January 2018, Brandi Bryant and her medical oncologist Rathi Pillai and radiation oncologist Kristin Higgins, had agreed on a plan: six rounds of chemotherapy and 30 rounds of radiation followed by 12 months on immunotherapy.

This was standard and was considered a curative approach, Pillai says.

As she neared the end of radiation, though, Bryant was so weak she couldn’t climb stairs, couldn’t brush her toddler’s teeth, couldn’t even sit with her kids for more than a few moments. To make matters worse, what had been a small pericardial effusion, a sack of fluid surrounding her heart, had grown so large that it now required an operation.

Surgeons were able to drain the fluid, but when they tested it, they found more cancer.

Days later, her cancer was reclassified to recurrent. Ironically, this opened a door for Bryant. A biopsy found that her tumors had a genetic rearrangement in a gene called ALK (anaplastic lymphoma kinase),

“This grant will spark new ways of thinking about the problems our patients face.”

Wally Curran Winship Executive Director

Lung Cancer SPORE leaders (left to right): Douglas Graham, Rafi Ahmed, Madhu Behera, Wally Curran, Taofeek Owonikoko, Michael Kutner, Adam Marcus.

[ Winship Magazine

| 9 | Fall 2019

]

PHOTO BY KAY HINTON

Research ethicist Rebecca Pentz and team are conducting a study to determine how best to inform patients about “window of opportunity� trials that add to research knowledge.

The Deng lab is focused on one of the most common mutations driving lung cancer, in the K-ras gene. Here, Dongkyoo Park prepares lung cancer cells to be radiated.

Taofeek Owonikoko examines lung cancer patient Michael Winship.

[ Winship Magazine

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Winship’s Lung Cancer which is only present in about 4 percent of lung cancers.

Winship’s Lung Cancer Tumor Board discussed the different options: stick with the original treatment plan, which included immunotherapy, or start her instead on a targeted therapy aimed at ALK. Bryant knew that immunotherapy had produced stunning improvements in some patients, but for many others it did nothing at all. Pillai came down on the side of targeted therapy, recommending a drug called alectinib.

Radiation had irritated Bryant’s esophagus and left her weak and unable to manage solid foods. She didn’t start her first pills until May. But soon, she could sense a change. “I knew something was working,” Bryant says. “I could tell the tumor was shrinking.” As the weeks went by, she began to feel better and better—less fatigued by the daily chores, more like the healthy person she’d always been. She began to walk up stairs again, and took a trip to see family in Oklahoma with all four kids. “Look at me getting my Independent Woman badge back,” she wrote on her blog.

Then, on October 1, exactly five months after she’d started on alectinib, a scan came back with stunning news: no evidence of disease. Bryant was ecstatic.

“Hooray!!” she wrote on her blog. “No active cancer, everything looks good!”

For Bryant, targeted therapy has done wonders. Unlike chemotherapy, which kills cancer cells and normal cells, the targeted therapy blocks growth signals that are specific to her cancer cells. Targeted therapies have become a cornerstone of precision medicine. But there’s a catch: they only work for so long. Eventually, a patient’s tumors can become resistant to the drugs, rendering them ineffective.

The hope for patients like Bryant is that by the time that window closes, there will be something else. A year later, she continues to take alectinib pills.

“Four in the morning, four at night,” she says with a chuckle, reciting her daily regimen. “And always with food!”

Tumor Board discussed different options: stick with the original treatment plan, which included immunotherapy, or start her instead on a targeted therapy aimed at ALK.

In the fall of 2017, Ramalingam and colleagues reported the results of a landmark study of the drug osimertinib, a targeted therapy developed for the treatment of non-small cell lung cancers with mutations in the epidermal growth factor receptor (EGFR) gene. In lung cancers, mutations in the EGFR gene are more common than in ALK (15 percent compared to 4 percent).

What makes osimertinib exciting is that it blocks not only the EGFR pathway but also another pathway cancer cells use to escape and develop resistance—a kind of backstreet the tumor takes when the freeway is closed. “With osimertinib, you could block both of those roads at the same time, and that results in better outcomes,” Ramalingam says.

Osimertinib stops tumors from progressing for almost twice as long as previous therapies. Still, cancer seems always to find another way.

“Once osimertinib fails, the patient has to go on chemotherapy,” says Taofeek Owonikoko, a medical oncologist specializing in lung cancer.

With support from the Lung Cancer SPORE, Owonikoko is collaborating with Douglas Graham, chief of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, to probe a third pathway, called MER, which comes into play when EGFR is blocked. Early findings [ Winship Magazine | 11 |

Fall 2019

]

Bryant knew that immunotherapy had produced stunning improvements in some patients, but for many others it did nothing at all.

Ahmed says several factors may explain why immunotherapy drugs aren’t effective for most lung cancer patients.

“The first priority is understanding how it’s working, why it’s working, and then see when it’s not working, what’s missing. Otherwise you’re in the dark.”

Rafi Ahmed Director, Emory Vaccine Center Lung Cancer SPORE investigator

indicate that MER is active in the tumor microenvironment, where it suppresses the body’s innate immune response. That suggests that blocking the MER pathway might sensitize EGFR-mutated tumors to osimertinib, enhancing that drug’s effect.

Graham and Owonikoko are conducting a clinical trial that combines osimertinib with a new targeted therapy, which was designed to block the MER pathway. That drug, developed in Graham’s lab, is already being studied at Winship in clinical trials.

The SPORE will build on this by developing a trial combining osimertinib with the MER inhibitor. If successful, the combination trial could lead to a more effective approach to overcoming resistance to osimertinib.

“We’re really excited about this work, which has direct implications for our patients, both in terms of quality of life and longevity,” says Owonikoko.

The Lung Cancer SPORE grant is also supporting basic scientists as they go back to the lab and look for other ways to target mutations in lung cancers. Xingming Deng, a leader in developmental therapeutics, and his colleagues are focused on mutations in the gene K-ras, one of the most common mutations driving lung cancers (more than 25 percent). They have developed a compound that could sensitize cancer cells to radiation by targeting a molecule activated by K-ras, thought to be “undruggable” until recently.

The need for more answers and more options is urgent. Winship physicians treat many lung cancer patients who don’t benefit from the new therapies. Michael Winship is one of them.

[ Winship Magazine | 12 | winshipcancer.emory.edu ]

Michael Winship was at the beach for a long Labor Day weekend when a friend noticed a lump on his shoulder.

It had been years since Winship, 57, had seen a doctor, but he happened to have an upcoming appointment about an issue with his blood pressure.

“I showed the lump to the doctor, and she immediately ordered a CT scan,” he says. The next day he learned he has small cell lung cancer.

Winship was referred to Owonikoko, who promptly started him on radiation and chemotherapy—and that worked well.

But once Winship completed the regimen, the tumor on his shoulder began to grow back. “That’s when they switched me to immunotherapy.”

Immunotherapy did not work for him and Owonikoko returned to the drawing board. In the months since, Winship has started another chemotherapy regimen.

Patients like Michael Winship show the limitations of the current therapies and spur the work of Winship’s Lung Cancer SPORE.

In an effort to bring the sometimes astounding results of immunotherapy to more people, Ramalingam is teaming up with renowned immunologist Rafi Ahmed, director of the Emory Vaccine Center.

Ahmed says several factors may explain why immunotherapy drugs, known as checkpoint inhibitors or PD1 blockers, aren’t effective for most lung cancer patients. They work by “waking up” some of a patient’s T cells, an attack arm of the immune system, which have been pushed into dormancy by prolonged contact with cancer. But if there aren’t enough T cells that recognize

the tumor to start with, or if the tumor is immunologically not open, that could limit an effective response.

“We are trying to overcome this by using combination therapy,” Ahmed says.

“We use PD1 blockade to release the brakes on the T cells, but then provide other factors so that the tumor microenvironment is receptive.”

Several years ago, Ahmed’s lab had observed that certain drugs (paradoxically used as immunosuppressants) actually stimulate the long-lived “stem-like” T cells responsible for immunological memory in animal models. The new SPORE will allow researchers to test the effects of combining those drugs with checkpoint inhibitors for a limited time in lung cancer patients before surgery.

Working with Ahmed, Ramalingam and colleagues have already shown that patients whose T cells display a strong proliferative response to checkpoint inhibitors do well later. Recent research suggests that the responsive T cells aren’t in the tumor already, but are waiting elsewhere in the body.

“We need to know more about where the stem-like T cells live, and how they respond to immunotherapy,” Ramalingam says. “The labeling experiments that we plan to conduct as part of the SPORE will be highly informative.”

Scientists are planning innovative experiments, using “heavy water” non-radioactive labeling, which will help them track the T cells that checkpoint inhibitors unleash. Through the SPORE’s multidisciplinary approach, Ahmed says, “We can

Jennifer Carlisle uses a fluorescence-activated cell sorting (FACS) machine to separate out the T cells that are responsive to checkpoint inhibitor immunotherapy drugs.

Researchers in Rafi Ahmed’s lab, Sakshi Malik (left) and Don McGuire, Jr. (right) are looking for patterns of gene activity in T cells.

begin to answer some of lung cancer’s most pressing questions and generate new ones that each of us, working alone, might never have thought to ask.” w

[ Winship Magazine | 13 |

Fall 2019

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TARGETING

METASTASIS THROUGH METABOLISM

by QUINN EASTMAN

illustration by christiane beauregard

At your last visit to the dentist, you may have been given a mouth rinse with the antiseptic chlorhexidine. Available over the counter, chlorhexidine is also washed over the skin to prepare someone for surgery. Winship Cancer Institute researchers are now looking at chlorhexidine and its chemical relative alexidine for another purpose: stopping cancer metastasis.

W

hile the researchers don’t envision using chlorhexidine mouthwash as an anti-cancer measure directly, their findings suggest ways to combine other drugs, already in clinical trials, in ways that could deplete the cells needed for metastasis.

When used as an antiseptic, chlorhexidine is basically a detergent that blasts bacteria apart, scientists think. As leads for potential anti-cancer agents, chlorhexidine and its relatives appear to have a different effect. They interfere with mitochondria, the miniature power plants in our cells. Cancer cells trying to metastasize and invade other tissues seem to need their mitochondria more—especially those cells that are leading the way.

Chlorhexidine and alexidine emerged from a search, or screen, by Adam Marcus and colleagues for drugs that can preferentially target “leader cells” more than “follower cells.” In research published in 2017, Marcus’ lab showed that the leaders and followers depend on each other for mobility and survival.

(A video of researchers separating out leaders and followers from metastatic cells is on the Marcus bio page on the Winship website.) The leaders are more mobile and have a distinctive shape, while the followers proliferate more steadily. More recently,

researchers used leaders and followers to test many potential drugs, looking for chemicals to which the leaders are more sensitive.

“One of the things we learned from our drug screen is that leader cells are difficult targets,” Marcus says. “They were resistant to most of the compounds that we threw at them. But it does look like we can specifically go after their metabolism.”

Mitochondria vs. glycolysis In general, cancer cells are known for having a sweet tooth—they take up glucose (blood sugar) more than normal cells, and depend on the process of glycolysis, or breaking down glucose. This tendency is called the Warburg effect, after Nobel Prize winner Otto Warburg. He observed that cancer cells rely on the process of glycolysis, which takes place outside mitochondria and doesn’t require oxygen.

What Marcus and colleague Mala Shanmugam show in an upcoming manuscript is that leader cells are less sugar-hungry than follower cells. They use more oxygen and depend less on glycolysis than followers. What is the explanation for the link between mitochondria and metastasis?

Leader cells may depend on mitochondria for energy and other signals to sustain their invasive behavior, Marcus says.

[ Winship Magazine

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Chlorhexidine and alexidine can push leader cells into relying more on glycolysis, and thus into acting like follower cells. The compounds can stop many types of lung and breast cancer cells from behaving invasively, the Winship researchers found. Alexidine was even more potent than chlorhexidine.

The drug screen was conducted in cooperation with Winship researchers Haian Fu and Yuhong Du, and Emory’s Chemical Biology Discovery Center.

Marcus says both alexidine and chlorhexidine, which share part of their chemical structure, dial down the activity of an enzyme called PDH (pyruvate dehydrogenase), a sort of control valve that governs how much fuel is sent into mitochondria versus glycolysis. As it turns out, PDH is the target of a separate drug that also suppresses invasive behavior and is already in clinical trials for several types of cancer.

Marcus and Shanmugam are not the only scientists who have become interested in alexidine recently. Several labs around the world have identified alexidine as an agent capable of targeting mitochondria. Winship researcher Cheng-Kui Qu and colleagues obtained similar results with alexidine in an investigation related to bone marrow transplantation.

The other members of the invasive pack, follower cells, have their own particular sensitivities. Since they depend more on glycolysis, they are vulnerable to drugs that block glucose intake. Marcus and Shanmugam tested one that was recently discovered by the German firm Bayer; they observed it could work together with either alexidine or another trial drug to preferentially kill lung or breast cancer cells. “For the first time, this gives us the ability to target two distinct cell populations that seem to cooperate to drive metastasis,� Marcus says.

With initial support from the Georgia Research Alliance, Marcus recently received funding from the Coulter Translational Fund to continue developing alexidine and create related compounds, with an eye toward commercialization. w

“Can you help me live?”

Everyone’s cancer journey is different, and yet patients describe similar feelings–the stomach-dropping moment of hearing a cancer diagnosis, the roller coaster ride between hope and despair, the intense gratitude they feel for those who care for them.

This photo essay was shot in some of Winship’s outlying clinics.

In paying tribute to people who deliver great nursing care,

we want to show where hope lives.

Emory at Buford nurse

Caitlyn Ciochetti

patient

Marcia Causey

Tuesdays are Marcia Causey’s “special” days, when she goes to the Winship at Buford clinic and sees nurse Caitlyn Ciochetti, who’s taken care of her since her ovarian cancer diagnosis in 2017. “John (husband) gets me coffee, I see Caitlyn, I have a little cry, and then we get on with it!” She says her team at Buford go above and beyond to help her. “I try to have a smile because so many with cancer have it so much worse than me! My goal is to help others dealing with cancer.

It is not always a death sentence and it makes every day count.

Never give up.”

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“If I can help one person by saying one positive thing about my stage IV life changing experience it will be worth it.” —Marcia Causey

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Emory Saint Joseph’s Hospital infusion nurse Debbie patient

Yang

Kewanna Royster

When Kewanna Royster was about to start chemotherapy treatment for breast cancer in August 2018, she asked for a very special kind of person to be her nurse–someone who is patient, someone who would smile even when it was grim, and most important, someone who believes in God and would pray with her. She found all that in Debbie Yang.

Royster says Yang has built her hope back up. Their shared spirituality gives them a special bond, inspiring them to pray together over the chemo drugs, and Royster says “Debbie sees me through God’s eyes.” Debbie Yang returns the love: “You make me feel valuable.”

Shared spirituality gives them a special bond.

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“It’s been rough, a real roller coaster but I’m almost at the end now.”

—Cordella Samborne Darkin

Emory Saint Joseph’s Hospital radiation oncology nurse Michele Rutherford patient

Cordella Samborne Darkin

Cordella Samborne Darkin was diagnosed with breast cancer a year ago. She underwent chemotherapy, lost her hair, and then started radiation therapy. She says the radiation staff go out of their way to make her comfortable, but she has a special bond with nurse Michele Rutherford, who lifts her spirits by wearing pink scrubs, Darkin’s favorite color. “It’s been rough, a real roller coaster but I’m almost at the end now.” And, she’s happy that her hair is growing back.

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Emory Johns Creek Hospital nurse

Tony Zanardo

patient

Kirk Stephens

Kirk Stephens says his care team at Emory Johns Creek Hospital has become family to him and his wife, Jennifer, as he’s undergone 40-plus rounds of chemotherapy as well as radiation therapy. Infusion nurse Tony Zanardo has cared for Stephens from day 1 when he started treatment for stage IV colon cancer. The Cumming native says the team’s personal touch has helped pull him through: “These people are amazing. Tony even calls me after hours if needed. I can’t imagine what it would have been like without that care.” w

Kirk Stephens says his care team’s personal touch has helped pull him through.

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CONNECTING WITH THE COMMUNITY

A

PHOTOS BY ANN WATSON

PHOTO COURTESY ATLANTA DREAM

s head coach of the WNBA’s Atlanta Dream women’s basketball team, wins and losses matter a lot to Nicki Collen.

But when her sister died five years ago from cancer, her perspective changed. “It made me think about where I was in my life and it has really driven a lot of the decisions I have made,” she says. “Now, I only do things that I am really passionate about and cancer research is one of them.”

That was the motivating factor behind Collen’s decision to become this year’s grand marshal of the Winship Win the Fight 5K which has raised more than $800,000 to date for cancer research that stays right here in Georgia. Collen explains: WNBA Coach of the Year and her team set a franchise record “In coaching, people don’t care about how much you know until with 23 wins and a trip to the WNBA Playoffs. they know about how much you care. A big part Collen calls women’s basketball a grassroots effort of caring about people is caring about the commuch like raising money for cancer research. She “Now, I only do munity and being connected.” appreciates that the Winship 5K promotes good health things that I am Collen is in her second season leading the and healthy habits, both keys to helping prevent cancer Atlanta Dream. In 2018, she was named the really passionate in the first place. “There are things you can’t control in your life and one of them is losing someone you are about and cancer really close to. It made me examine things that I can research is one control, like my health, cooking healthy food for my family, and being active.” of them.”

She says: “Cancer research may not affect every single person in their lifetime, but ultimately, it’s going to affect their kids and their kid’s kids. Doing something for the greater good is the most important thing for me. I am just excited to see where cancer research goes.” w

Coach Nicki Collen visits Winship patients in the infusion center: LuDella Gilmore (top), Stephen Padgett (middle), Dorothea Green (bottom), and Nicole Iris Anderson (above). [ Winship Magazine

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1

RUN TO WIN 2

3

1. Runners and walkers crossed the start

funds for cancer research at Winship,

$800,000 to date and donations will be

line on Oct. 5 for the ninth annual Winship

including a newly endowed professorship

accepted until Nov. 29.

Win the Fight 5K. The event drew 3,500

to support Winship investigators explor-

participants and 400 volunteers to the

ing new areas of cancer research. This

Emory campus. The Winship 5K raises

year’s Winship 5K has raised more than

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2. Team spirit was super strong this year from top Winship 5K corporate sponsor Peach State Truck Centers. ]

4

N

5

PHOTO BY PETE WINKEL

7

6

3–6. The Winship 5K brings

5K Grand Marshal Coach Nicki Collen;

together families, friends, students,

Winship Executive Director Wally

supporters of all ages.

Curran; Emory President Claire

7. The pre-race program was kicked off by (left to right) WSB-TV reporter and 5K Emcee Mark Winne; Winship

8

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Sterk; and Emory Healthcare CEO Jon Lewin.

8. Survivors made the day shine.

Mapping a calmer passage T H R O U G H I FIRST MET WINSHIP ONCOLOGIST DR. KEITH DELMAN NINE YEARS AGO, after my best

friend insisted that the persistent small spot on my face should be checked. Turns out it was melanoma, and I was scared.

Anxiety was not like me. I was a deadline journalist, focused under pressure. I grew up playing competitive golf, performing in an unforgiving spotlight.

Cancer didn’t run in my family, and I had imagined a long life with my children. But I couldn’t visualize what was going to happen to me, and the more I tried, the more anxious I became.

In the mirror, the cancerous spot on my left cheek looked like a pink pencil eraser.

But a lot more than the spot would need to go. Dr. Delman planned to remove a chunk of tissue the size of a golf ball. A golf ball!

My diagnosis felt like a bad debt from all those hours in the sunshine playing golf before sunscreen was common.

As my surgery approached, I looked for anything tangible that would give me

“Soon after the surgery I learned that my melanoma had not spread.

I could let go of my fear.

I had arrived safely.”

—Michelle Hiskey patient

strength and comfort.

I had noticed the necklace that Dr. Delman wore, a small green circle containing a beautiful map of water and land, and I asked him what it signified. He told me it was a navigational map, a memento of his time as a ferry boat captain in the Great

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CANCER

South Bay around Long Island, New York. Taking vacationers back and forth across the shoals was how he paid for medical school at nearby Stony Brook University.

In the Great South Bay, the depth of the water changes all the time, sometimes dangerously, and the weather can be hazardous. Dr. Delman knew what was under that water and how to maneuver in every condition. His passengers always arrived safely. This reassured me.

SOON AFTER THE SURGERY I LEARNED THAT MY MELANOMA HAD NOT SPREAD.

I could let go of my fear. I had arrived safely. Almost a decade later, I remain cancer-free. As Dr. Delman predicted, the 60 stitches on my cheek have faded into my smile lines. Look closely, and

“Knowledge is power, and understanding is critical.”

—Keith Delman Specialist in minimally invasive surgery for melanoma

you’ll see that my scar is shaped like a question mark, apt for a journalist.

Recently, as I reconnected with Dr. Delman while preparing to write this story, I asked him for any advice that would help anxious cancer patients. He said that a cancer diagnosis doesn’t need to send patients reeling. Instead, the diagnosis should be part of a bigger story of possibilities.

“A cancer diagnosis is someone’s worst day ever. That said, we’ve done a really bad job putting cancer into context,” he said. “Many cancers are curable, like yours was. In contrast, high blood pressure is incurable, yet no one cries when they get that diagnosis. Knowledge is power, and understanding is critical.”

Cancer tested my ability to trust. My scar reminds me of that, and the rough waters that I could not cross without expert navigation.

“Get a great team and put the worrying in their hands,” Dr. Delman added.

“Make plans in the same way that you wear a seatbelt: You’re prepared for an accident, but you don’t worry about it every minute of every drive.”

I see what he means. If you’re anxious about your diagnosis, I hope you can see it too.

Michelle Hiskey today supports Winship Cancer Institute as a grateful patient and as a project manager with Emory Advancement Communications, a creative team that serves donors across the university. Her digital story, “Necklace Man,” can be viewed at emry.link/necklaceman. w

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TEAM WORK

PHOTO BY BECKY STEIN

Lung Cancer SPORE team members