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SUMMER 2021

SPECIAL ISSUE

MSKNewsMEMORIAL SLOAN KETTERING CENTER Defeating Cancer’s Spread On the 50th anniversary of the War on Cancer, this SPECIAL ISSUE focuses on : What’s available now — and on the horizon — for patients like Ilene Thompson facing advanced disease.

ALSO INSIDE:

A Major Advance for Patients

Seed and Soil: A ’s Journey

How to Outsmart Tumor Evolution TABLE OF Dear MSK Community,

These are the four most frightening words for a patient to hear: “Your cancer is back.” CONTENTS

As we mark the 50th year of the War on Cancer and look to the future, our mission at Memorial Sloan Kettering is nothing less than conquering the most urgent challenge: preventing cancer’s spread. Also called metastasis, it causes 90 percent of cancer deaths. It’s why we are devoting this entire issue to reporting on how we offer hope and help to patients whose cancer has spread. 12 Metastasis: A Roadmap In the clinic, we are developing more targeted drugs, more precise radiation, and more sophisticated See the journey of a cancer cell as it transforms surgical techniques to treat our patients. In the lab, we are learning more every day about why and travels through the body. cancer cells metastasize and how to stop them. Our vision to save more lives requires a commitment to hire and train the brightest minds Multiplying the Army and a significant investment in four key areas of technology, which are already bringing about 17 astonishing advances: of Cancer-Fighting Immune Cells • Better models to study cancer: Conducting research in mice is time-consuming and doesn’t Learn about a new technology taking necessarily reflect cancer biology in humans. New technology makes it possible to grow samples immunotherapy to the next level. It multiplies of a patient’s own tumor in a dish in order to understand its evolution and test its response to an army of cells to seek out and destroy a cancer drug — getting results faster than ever before. 4 8 metastases anywhere in the body. • Visualizing cancer at every level from atoms to organs: State-of-the-art imaging equipment A Major Advance Seed and Soil can be used to visualize single cells moving and reacting in real time; observe how cancer cells MSK researchers are learning Radiation Reimagined behave and find them before they take root in new places; inspect fragile tissue samples; Finds Hidden 18 more about how cancer cells Meet the specialists at MSK who are pioneering and spot tumors in the body. Prostate can survive undetected for the use of potent, knifelike beams that can sear Cancer Cells years only to return in new cancer cells and spare healthy tissues to give • Analyzing cells one at a time: We’ve made great progress understanding how genetic mutations A transformation is coming places. These insights will our patients a second chance — with fewer can drive . But they don’t account for all tumor behaviors, particularly metastasis. in how prostate cancer guide future therapies. side effects. Sophisticated equipment helps us understand how cancer cells adapt to new environments is identified and treated, as they break free from their original tumors. even after relapse. MSK researchers are leading • Using computers to decode cancer’s behavior: Through all of our new technologies, we are A New Frame of Mind the way. 20 MSK doctors are treating metastatic brain cancer gathering more data than ever before. We need to improve our computational methods to aggressively and getting good results. organize, describe, and find patterns in this data that can unlock the reasons cancer spreads.

Our patients choose MSK because our compassionate care is powered by innovative research that we conduct through a major investment of resources. Our scientists and physicians have helped 22 Always by Your Side develop and test groundbreaking drugs, immunotherapies, surgical and radiation Deep relationships in our support techniques, and countless other treatments that have saved lives. And we share our work with the world. groups are another form of treatment. We know that with enough resources, we will stay on a path of relentless discovery, leading the way and protecting our patients from hearing those four frightening words. BACK COVER Two Visionary Donors Are Changing the Way Metastasis Is Studied at MSK His Cancer Spread Much of the work described in this issue reflects 14 Three Times the pioneering efforts of the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center When cancer cells change, special testing enables new (GMTEC). Founded in 2017 with generous support therapies to keep the disease at bay. Garth Atchley was from Alan and Sandra Gerry, GMTEC fosters diagnosed with that spread to his brain four pathbreaking research by investigators across CRAIG B. THOMPSON LISA DEANGELIS JOAN MASSAGUÉ years ago, and he’s still running marathons. MSK. Learn more about how the Gerrys have President and Physician-in-Chief and Director, accelerated metastasis research. Chief Executive Officer Chief Medical Officer Sloan Kettering Institute

Read more stories online: mskcc.org/summer-2021 | 3 A Major Advance Tracking and Treating Hidden Prostate Cancer Cells

A transformation is coming for patients with prostate cancer, says Memorial Sloan Kettering medical oncologist Michael Morris. Researchers at MSK have helped pioneer major advances that will enable doctors to pinpoint the location of prostate cancer cells more precisely than ever before so they can be targeted with personalized treatments. The researchers also have begun to solve an enduring mystery about how some metastatic prostate cancers escape powerful drugs.

The most immediate breakthrough than we could with standard CT or involves a new form of imaging. PET scans,” he says. Dr. Morris played “This is the biggest diagnostic advance a leading role in clinical trials testing for prostate cancer since the 1980s, when a particular tracer that is easy to the PSA [prostate specific antigen] test manufacture and can be used at all was introduced,” Dr. Morris says. “Imaging institutions. MSK radiologist Hebert has been the Achilles heel of prostate Alberto Vargas and interventional cancer because the disease is hard to radiologist Jeremy Durack were key detect after it has spread, forcing many collaborators in the development and treatment choices to be based on estima- testing of the tracer. tion and probabilities. Now, we can be In May, the FDA approved this tracer much more confident that we are correctly — the first for national, widespread use. identifying the location of the disease to The PSMA advance is the result of years make an accurate treatment plan.” of work by MSK’s Molecular Imaging and “I had no side effects either on the day of the The new technology uses a radioactive Therapy Service, led by Heiko Schöder. procedures or afterward. My PSA went right substance that selectively seeks out and This technology has an even more attaches to a specific protein on the cancer exciting potential: zeroing in on prostate down, and my tests have been really good. cell surface. The protein, called prostate- cells to destroy them. A therapy called specific membrane antigen (PSMA), is not 177Lu-PSMA-617 selectively binds to From how I feel today, you would never think found on most normal cells. When the PSMA in prostate cancer cells and I had cancer a few years ago.” radioactive tracer binds to the prostate delivers DNA-damaging radiation, killing cancer cells, they show up as bright spots the cell. Patients receive this treatment —Michael Rosenblum, MSK Patient on a PET scan. by injection over six sessions, usually “With PSMA PET, we can now detect spaced six weeks apart, given by nuclear the cancer cells directly and much earlier medicine physicians.

4 | MSKNews Read more stories online: mskcc.org/summer-2021 | 5 “Effective treatments for metastatic June. Men who received the drug had a resistance, based on lessons he learned prostate cancer have been limited, so this median of 8.7 months of progression-free from pioneering the lifesaving treatment could be a game-changer,” Dr. Morris says. survival — the period when the disease imatinib (Gleevec®) to treat chronic Just ask Michael Rosenblum. In 2019, didn’t worsen — compared with 3.4 myeloid (CML). Imatinib targets his prostate cancer had become resistant months for those receiving only standard an abnormal protein and essentially cures to treatment and had spread to his . treatment. Side effects were not serious. CML — a landmark in targeted cancer therapy. His PSA levels — a marker that normally Among the most common was dry mouth. But Dr. Sawyers discovered cancer should be in the single-digit range — had “We hope this therapy will receive cells could become resistant to imatinib. soared to more than 100. FDA approval,” says Dr. Morris, whose This raised the question of whether a Dr. Morris enrolled Michael in a clinical research has been supported by the different mechanism had taken over to trial led by nuclear medicine physician philanthropy of the Magnier family. promote the cancer. Researchers wondered Lisa Bodei testing the benefits of 177Lu- For Dr. Morris, the recent inroads if they were still focused on the right target. PSMA-617 when used in combination against this stubborn disease — the Dr. Sawyers’ instincts told him to zero in with standard prostate cancer therapy. second leading cause of cancer death in even more closely on the abnormal protein, Since Michael’s last treatment in February men — are especially gratifying. believing it was the scene of the crime. 2020, the 75-year-old has been free of “I have been involved in the PSMA “When you play the game Clue and symptoms. His scans have improved, and research since the end of my fellowship at think the murder happened in a certain his PSA is less than 1. He just celebrated his MSK in the late 1990s,” he says. “The benefits room, that’s the room you go to,” he says. 50th wedding anniversary. these advances will bring to men with this “With CML, we discovered that we had “I had no side effects, either on common disease cannot be overstated.” the right target but that the protein was the day of the procedures or afterward,” mutating. It didn’t completely solve the Michael says. “My PSA went right down, problem, but it led to important insights and my blood tests have been really good. Escape Artists into how resistance develops.” From how I feel today, you would never Another promising effort to help patients Dr. Sawyers says he remembered think I had cancer a few years ago.” with metastatic prostate cancer is being this lesson when his research shifted to Physician-scientist Charles Sawyers found that some tumor cells can change their identity to evade Dr. Morris presented results from the led by physician-scientist Charles Sawyers, prostate cancer. He put a bullseye on treatment and survive. trial, involving more than 800 patients with the Marie-Josée Kravis and Henry R. Kravis a protein called the androgen receptor advanced prostate cancer, at the American Chair in Human and Pathogenesis. (AR), which all prostate cells — prostate Society of Clinical Oncology meeting in Dr. Sawyers is focused on fighting drug cancer cells in particular — need to survive Dr. Sawyers says he benefits greatly and grow. Staying focused on AR allowed from the expertise of MSK colleagues. researchers, including Dr. Sawyers, to For example, medical oncologist Charles develop several AR-blocking drugs Rudin had noticed similar plasticity in that have improved survival for advanced lung cancer cells — during treatment, the prostate cancer. tumors transformed from adenocarcinoma to small cell lung cancer. When the Identity Theft two researchers realized they had found “At one level, this is But some metastatic prostate cancers the same intriguing phenomenon, they still evade destruction. “We make smarter decided to collaborate to investigate it scary because it says that and more potent AR inhibitors, and the further. Dr. Rudin and Dr. Sawyers, along tumors still escape,” Dr. Sawyers says. with their lab members, began meeting a tumor has the ability to In the last few years, he and MSK regularly to trade notes and share insights. once again outsmart our “The benefits these advances colleagues have made a startling discovery: Dr. Sawyers’ team is also collaborating Some metastatic tumor cells actually with Sloan Kettering Institute computational drugs. But we really will bring to men with this biologist Dana Pe’er, a world-renowned change their identity to survive. This trans- understand this at a common disease cannot formation, known as lineage plasticity, expert in single-cell analysis. This powerful allows prostate cancer cells to no longer new technology enables researchers to much better level than we be overstated.” depend on the androgen receptor. look closely at individual cells to determine To undergo this change, the cancer which genes are expressed, or “turned on.” did just a few years ago.” —Michael Morris cells must have certain genetic mutations. This makes it possible to get a clearer Dr. Sawyers says focusing on those picture of how the mutations cause cells —Charles Sawyers mutations should make it possible to to change. know which patients will have cancers “This is similar to the challenges that are shape shifters. I faced earlier in my career with leukemia “At one level, this is scary because it in that we’re getting to that moment says that a tumor has the ability to once of clarity that will allow us to catch again outsmart our drugs,” Dr. Sawyers this transition in its earliest stages,” Dr. says. “But we really understand this at a Sawyers says. “That gives us a treatment much better level than we did just a few strategy for these prostate cancer patients years ago.” when the drugs stop working.” l

6 | MSKNews Read more stories online: mskcc.org/summer-2021 | 7 A Long and Difficult Road The need is painfully clear: Metastasis is responsible for 90 percent of cancer deaths. Once a cancer spreads, it’s nearly Like a dandelion impossible to contain. Seed Yet this depressing observation obscures seed, the odds a hidden silver lining: For all its deadly power, metastasis is not something that of a cancer cell cancer cells can do easily. Much like an individual dandelion seed, the odds of a metastasizing cancer cell metastasizing are not in its favor. and Soil Between dislodging from a and reaching fertile soil are many are not in its favor. Tracing the Journey of obstacles that a cancer cell must surmount. First, there is the powerful shear force Spreading Cancer Cells that comes from hurtling through the bloodstream. Then, there’s the challenge of finding an exit from that tumultuous flume ride: a tiny gap in a wall through which to crawl to relative safety. And that’s just one leg of the journey. Several years ago, Sloan Kettering The new environment itself presents Institute Director Joan Massagué and unfamiliar conditions. To survive — let his colleagues made a startling discovery alone grow and multiply — the would-be that explains how this could happen. They metastatic cell must be capable of found that dormant cancer cells have the For every windsurfing dandelion seed that adapting to its surroundings. That includes ability to cycle between periods of active lands in a nurturing spot and sprouts a new finding ways to dodge the searching division and a sleep-like state called quies- sensors of the immune system. cence. When the cells are actively dividing, weed, perhaps a thousand more will fall on Of course, considering the many millions they grab the attention of immune cells hostile ground or be trampled under foot. of cancer cells that break off from a primary called natural killer cells, which surround Something similar happens in cancer, which explains tumor every day, it’s not surprising that and kill them. But when cancer cells are why one of the most famous ways of thinking about its some do manage to clear all the hurdles. sleeping, they go undetected. The periodic cycling means that the spread is called the “seed and soil” hypothesis. First But to scientists seeking solutions, each of those hurdles represents an opportunity. lurking cancer cells are never killed articulated by the English surgeon Stephen Paget in completely, and the immune system puts 1889, the idea is that the ability of a cancer to spread Laying Low pressure on the surviving cancer cells to (metastasize) to other locations depends as much on the MSK researchers are especially keen to evolve new survival traits — including, even- tissue environment the cancer lands in — the soil — as understand what is, perhaps, the most tually, the ability to escape immune control. the character of the cancer cell — the seed — itself. confounding and frightening aspect of In alternating between periods of metastasis — how lone cancer cells can active division and dormancy, these rogue cancer cells resemble stem cells — This could explain, for tissue conditions but also the sometimes survive undetected in the body a population of cells that lives in and example, why breast cancers action of the immune system. for months and even years at a time helps repair tissues. tend to metastasize to bones In the past decade, re- without being killed, before eventually “Dormancy is a normal state for the and the lungs; why colorectal search from Memorial Sloan sprouting new tumors. Scientists call this stems cells in our body,” says Dr. Massagué, cancer tends to spread to the Kettering scientists has revolu- period dormancy. who holds the Marie-Josée and Henry R. liver; and why melanoma can tionized our understanding of Dormancy is difficult to study in people, Kravis Foundation Chair and is Executive spread pretty much anywhere. both the seed and the soil — but there’s no question it occurs. The most Director of GMTEC. “They stay dormant For many years, scientists and how the two interact to dramatic evidence comes from people until there is a need for their activity to focused most of their attention promote metastasis. With this who once had cancer, were cured, and then replace lost or damaged cells.” on the “seed.” They looked for new perspective, and support donated an organ. The organ recipient When cancer cells go dormant, they the source of cancer’s deadly from the Alan and Sandra then develops cancer — the very kind not only escape detection by the immune power in the genetic changes Gerry Metastasis and Tumor of which the donor was cured. The only system, they also evade being killed by occurring in cancer cells them- Ecosystems Center (GMTEC), possible explanation is that the donated treatments like chemotherapy, which work selves. But that approach tended MSK scientists are developing organ contained metastatic cancer seeds only against dividing cells. It’s a surprisingly to gloss over the importance of innovative strategies to stop that were lying dormant — perhaps kept in effective survival trait. the environment — not only local cancer’s spread. check by the donor’s immune system.

8 | MSKNews Read more stories online: mskcc.org/summer-2021 | 9 Turning Back the Clock Dr. Pe’er, a single-cell RNA seq expert as a pancreas or lung cancer cell could As Dr. Rudin and other MSK scientists Just this past year, Dr. Massagué’s lab — who collaborated on the study, thinks the possibly find itself in,” Dr. Pe’er says. “The are coming to learn, this identity switching this time in collaboration with the labs of lung cancer findings are likely to apply degree of adaptation that these cells must is not restricted to lung cancer. Almost computational biologist Dana Pe’er and across different cancer types. In fact, the undergo is extreme.” exactly the same switching is seen in physician-scientist Charles Rudin — study, which was published in Nature With physician-scientist Adrienne prostate cancer that is being treated with discovered another trick that cancer cells Medicine in 2020, served as the basis for a Boire, Dr. Pe’er is using single-cell analysis antiandrogen therapy and in breast cancer employ to spread. By studying lung cancer large grant awarded to MSK from the to explore these adaptations. They’ve that is treated with antiestrogen therapy. in mice and in human tissue samples, they Human Tumor Cancer Atlas Network, a already identified several that could be The findings have already changed found that lung cancer cells switch on National Cancer Institute-funded Cancer potential therapeutic targets. clinical practice. Now, when someone genes that are usually active only during Moonshot initiative. Dr. Pe’er and physician- relapses, doctors routinely re- the lung development. The cells in a sense scientist Christine Iacobuzio-Donahue, the Switching Tracks tumor to find out if it has changed. If it has, “go back in time” to an earlier stage David M. Rubenstein Chair, are the principal The shape-shifting quality that metastatic then they know to switch the treatment of development as they spread from a investigators. They are studying the tran- cancer cells exhibit may also explain some to match the new type of cancer. Clinical primary location to a distant site. sition from primary cancer to metastasis in cases of drug resistance. Several years trials are underway to test drug combina- Anna-Katerina “Kat” Hadjantonakis, lung, pancreatic, and colon cancers. ago, lung cancer specialists Helena Yu tions to prevent drug resistance. Chair of the Developmental Biology These organs share something in and Dr. Rudin began to notice that some of Program in SKI and Alfred P. Sloan Chair, common: They are all derived from their patients, when treated with drugs Outbreak remembers hearing about these discoveries the same layer of the embryo called called epidermal growth factor receptor After dislodging from a tumor, after for the first time. “Joan called me and said, the endoderm. (EGFR) inhibitors, eventually developed going dormant, after trying on different ‘We see this sequence of gene expression “Some of the nastiest cancers are resistance to these targeted drugs. But the identities, cancer cells must surmount one — does it mean anything to you?’ And those involving endoderm-derived organs,” way the tumors became resistant was final hurdle to spread: They must acquire I said, ‘Oh my gosh, this is the same says Dr. Pe’er, who is Chair of the Compu- unlike anything they had ever seen. The properties that allow them to grow in a sequence we see in an embryo as a tational and Systems Biology Program in cells transformed into an entirely different new territory. Karuna Ganesh, a Josie Robertson Investigator, in her SKI lab. lung forms.’” SKI, holds the Alan and Sandra Gerry type of lung cell that is not dependent on Tracking this last step has been the The tumors, in effect, “reenact the Endowed Chair, and is Scientific Director the growth receptor at all. focus of physician-scientist Karuna Ganesh, developmental program for making a of GMTEC. “For combating tumors derived “It’s as if the cell gets off one set of a Josie Robertson Investigator. In the past tissue, which is very dangerous for an lung, but out of time and out of place,” from these organs, understanding normal train tracks and jumps to a completely year, her lab found a particular molecule, organism. To repair this hole, tissues rely Dr. Hadjantonakis says. development is going to be critical.” different set,” says Dr. Rudin, theSylvia called L1CAM, appears to be required on stem cells that turn on a wound-healing A key technology for making this That’s why she and Dr. Hadjantonakis Hassenfeld Chair in Lung for metastatic cells to grow in a new program. Because cancer creates a wound discovery is called single-cell RNA seq (an are collaborating on a project to understand at MSK. “In order to make that switch, location. L1CAM was originally identified where it grows, it causes malignant abbreviation for sequencing pronounced the development of endoderm-derived tissues. the cells have to first go backward toward in the context of brain development. But cells to adopt this same wound-healing “seek”). It allows researchers to measure Dr. Pe’er and her colleagues are also a less differentiated state. And to do Dr. Ganesh’s research has shown that it behavior. It is these cells that will regenerate precisely which genes are turned on or looking at metastasis to the brain, which is that, they resort to some of the same also plays a crucial role in both colon repair the tumor. off in individual cells among thousands of dramatically different than other organs. developmental genes that we also see being and in colon cancer. “Metastasis is wound healing gone cells all at once. “The brain is as foreign an environment turned on in the context of metastasis.” In a normal colon, activating L1CAM in wrong,” Dr. Ganesh says. tissue stem cells is part of the way that the By learning more about the ways that colon repairs itself after an such cancer cells repurpose these and other Physician-scientist Charles Rudin as colitis. Stem cells making L1CAM can properties of stem cells, researchers hope The goal of MSK separate from their neighbors, migrate to throw up barriers to metastasis. into the gap of a wound, and then start “My dream is that the research being researchers is to turn to fill it in with healthy new cells. done now on dormancy and outbreak But L1CAM also permits metastatic will lead to therapeutic breakthroughs,” metastatic cancer into cancer cells to repair the tumor — and Dr. Massagué says. “One possible approach a manageable chronic regenerate it in a new location. In fact, might be to trick the dormant cells into cancer cells can’t grow without it. The expressing those genes that alert the condition and, perhaps researchers can see this when they knock immune system so they are eliminated out L1CAM in tumor cells growing in mice. the same way that 99 percent of their one day, uproot cancer The cells are able to seed new areas, but comrades were eliminated.” for good. they do not germinate. With L1CAM, He hopes that learning more about however, the cells begin to crawl along the steps that lead to metastasis in the first blood vessels and make themselves at place will also help physicians understand home in their new location, eventually what happens when cancers relapse. forming a new tumor. Based on this Over the next decade, with the help insight, Dr. Ganesh’s lab is actively looking of sophisticated new technologies, MSK for drugs that could block L1CAM. researchers plan to mount a concerted The fact that metastatic cancer cells attack on the problem from all sides. co-opt the body’s wound-healing system Their goal is to turn metastatic cancer into is devilish but also makes a kind of twisted a manageable chronic condition and, sense. A wound is essentially a hole in a perhaps one day, uproot cancer for good. l

10 | MSKNews Read more stories online: mskcc.org/summer-2021 | 11 Metastasis: A Roadmap Metastasis — the spreading of cancer from its original location to a new location — can be broken down into three main stages: dissemination, To learn more and see dormancy, and outbreak. Memorial Sloan Kettering researchers at the an animation, scan here Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center are making advances in understanding each of these three stages.

1 Dissemination 2 Dormancy 3 Outbreak

Cancer cells continually break o from Treatment can kill most of these cancer Over time, these escapee cells develop original tumor and enter blood circulation. cells, but some survive and go dormant, like traits that enable them to adapt and Most die, but some may linger in the body seeds. Dormant cells periodically wake up survive in a new location. They cling to for months to years at a time. and start to divide. The immune system blood vessels and trick the body into sees and kills these dividing cells, but thinking they are a wound that needs dormant ones escape. to be healed. This is how metastatic tumors grow.

Original breast tumor Metastatic tumor Immune cell

Original tumor

Dormant metastatic “seed”

Cancer cell Metastatic tumor

1st Treatment 2nd Treatment 3rd Treatment

MONTHS TO YEARS

12 | MSKNews Read more stories online: mskcc.org/summer-2021 | 13 considered standard therapy,” Dr. Yu says. Garth. MSK-IMPACT and other genetic “Molecular testing is a crucial part of tests enable patients to be matched with figuring out those next steps.” targeted therapies that counteract the mu- Shortly after Garth’s tumor samples tations driving the growth of their tumors. were submitted for testing, he was walking Unfortunately, though, tumors often find near his office in Midtown Manhattan, where ways to stop responding to medication. he works for a global shipping and logis- “Tumors learn from the very beginning tics company, when Dr. Yu called with the that the way to survive is by increasing first good news in weeks. His MSK-IMPACT their genetic diversity. We call this “Although I have stage results were not back yet, but another intratumor heterogeneity, and it is one IV cancer, Dr. Yu has preliminary molecular test had revealed his of the main drivers of resistance to His Cancer Has cancer had a mutation in a gene called therapies,” says MSK physician-scientist never talked to me EGFR. “She told me that having this muta- Pedram Razavi, who specializes in breast about . She Spread Three Times, tion was like winning the lottery,” he says. cancer. “The tumor’s ability to evolve is It meant he wouldn’t need chemo- the main challenge we have in treating has always been so but It’s Not Stopping Garth Atchley therapy. Instead, he immediately began metastatic cancers.” treatment with a targeted therapy Unfortunately, that’s what happened reassuring, letting me aimed at his mutation, a daily pill called to Garth. After 16 months on osimertinib, osimertinib (Tagrisso®). when he was feeling almost back to his know if something It also meant the radiation for his normal life, his cancer began spreading happens, there are more brain tumors could be scaled back to again. A biopsy of lymph node tumors just a few treatments. (Later, to destroy revealed an additional mutation. options that we can try.” cancer that had spread to his liver, Garth “When you learn your disease has also received selective internal radiation progressed, it’s scary,” Garth says. —Garth Atchley, MSK Patient therapy. MSK interventional radiologist “Although I have stage IV cancer, Dr. Yu Etay Ziv inserted small radioactive seeds has never talked to me about prognosis. through a catheter placed near the site She has always been so reassuring, letting of Garth’s tumor.) me know if something happens, there are more options that we can try.” Staying Ahead of Dr. Yu enrolled him in a trial for a Since being diagnosed with metastatic lung cancer, Garth Atchley has run three ultramarathons, two marathons, and several other races. He raises money Cancer’s Evolution drug called dacomitinib (Vizimpro®), which for Fred’s Team, which supports research at MSK. This photo was taken in front of MSK during the New York Road Runners NYC Half Marathon in March 2019. targeted the new mutation. It worked for Photo: Fred’s Team Molecular testing of tumors has made a monumental difference for people like an additional six months. But once more, Garth Atchley had just returned from a vacation to Yellowstone National Park with his wife and two teenage daughters when he realized something wasn’t right. The 47-year-old ultramarathoner didn’t have the energy to go running. He also felt unsteady on his feet, almost like he had vertigo.

He tried new glasses and saw a and immediately felt a rapport. She doctor for his allergies, but there was no explained that she would send a sample of improvement. So, he made an appoint- his for molecular testing ment with a neurologist near his home in with MSK-IMPACTTM. This test looks for Jersey City, New Jersey. An MRI revealed changes in more than 500 genes linked to devastating news: He had a brain tumor, cancer so patients can be treated with and it was metastatic — the result of an precisely the right drug. undiagnosed cancer that had started in Nearly four years later, Garth is his lungs. Just two days later, he had brain a testament to how far cancer science at a local hospital. has advanced to keep ahead of “When I look back now to that time, it cells that are constantly changing to feels like a blur,” Garth says. “My wife, Judy, outsmart treatment. and my sister-in-law, Mary, who is a nurse, stepped in and made sure that I was getting Targeted Therapies Lead the best care possible. They decided I to New Treatment Options needed to go to Memorial Sloan Kettering.” “Garth’s story illustrates the fact that On his first visit to MSK, he met we’re always trying to offer more for thoracic medical oncologist Helena Yu our patients — to go beyond what’s Medical oncologist Helena Yu specializes in finding the best targeted therapy treatments for people with lung cancer.

14 | MSKNews Read more stories online: mskcc.org/summer-2021 | 15 his cancer stopped responding. Doctors MSK has developed its own liquid biopsy then prescribed chemotherapy. Another test, called MSK-ACCESS, which looks biopsy of the lymph nodes in his armpit for more than 100 mutations in tumor MSK’s liquid biopsy test uncovered more molecular changes. The DNA in the blood. results were astonishing. He had lost the “Developing liquid is an looks for more than mutation that caused resistance to the first important part of our efforts in treating Multiplying drug — osimertinib — and picked up an- metastatic cancer,” Dr. Razavi says. other mutation that would make his “mira- “Being able to learn about cancer the Army of cle drug” work again. He’s has been taking mutations from a simple blood draw is his second course of osimertinib since easier for patients. Additionally, because Cancer-Fighting January 2020. His tumors have shown tumors that spread to different sites 100 no signs of further growth. may undergo different evolutionary mutations in tumor Immune Cells “I’m a big advocate of getting genetic pathways, liquid biopsies can often help DNA in the blood. testing more than once, especially if you us to get a more complete picture and have tumor progression or something else to more easily monitor the evolution of changes,” Garth says. “What I’ve learned the disease.” is that the mutations in your tumors are In addition to taking osimertinib, not always fixed.” Garth, who will turn 51 in July, now gets a low dose of chemotherapy every three “Treatment has given me the opportunity The Next Frontier of weeks. “I’m not totally used to it, but you to enjoy so many important things in my Molecular Testing get into a rhythm,” he says. “You know life,” he says. “Since we got married, my Although Garth was able to have multiple you won’t feel great for a few days after wife and I have gone to Long Beach Island, tissue biopsies, that’s not the case for chemo, so you just plan around it.” New Jersey, for two weeks every summer. many patients due to the location or Garth has resumed running and But for the past three years, we’ve rented a number of metastases. Liquid biopsies, now raises money for MSK through Fred’s place there for the whole season. My which can detect tumor DNA shed into Team. His family also goes camping several daughters have summer jobs on the the bloodstream, are a promising new times a year and hiking whenever they island, and they get to spend time with advancement for addressing that need. get the chance. their friends. It’s really our happy place.” l

Physician-scientist Allison Betof Warner is leading a trial of a new immunotherapy for melanoma that has spread to the brain.

Using patients’ own immune systems tumors to be grown outside the body Medical oncologist Adam to fight cancer has been one of the in large numbers. Schoenfeld is leading another trial most exciting advances in cancer Investigators at Memorial Sloan for TIL therapy at MSK, which treatment over the past decade. Kettering are conducting clinical includes patients with several types Now, a new immunotherapy could trials for TIL therapy, which is being of metastatic disease, including take this approach to the next level. considered for approval by the US lung and head and neck cancers The treatment, called tumor Food and Drug Administration later and melanoma. infiltrating lymphocyte (TIL) therapy, in 2021. “We are in early-phase trials in harnesses and expands the power of Physician-scientist Allison Betof lung cancer, but I believe this treatment immune cells that have already been Warner is leading the development of could be a potential breakthrough fighting the cancer. The patient’s TIL therapy for metastatic melanoma for patients — especially those who immune cells are removed from at MSK, including an upcoming study have disease that’s resistant to immu- their tumor after surgery, given a that will be the only trial to specifically notherapy — when treatment options treatment that makes them multiply, evaluate this approach in melanoma can be limited,” Dr. Schoenfeld says. and then infused back into the body that has spread to the brain. “When “While there are several different where they can seek out and destroy melanoma spreads, it often goes to steps required for TIL therapy, which remaining metastases anywhere in the brain, but patients with brain can be challenging for patients to go the body. metastases are usually disqualified through at times, the side effects The concept of TIL therapy is from participating in clinical trials tend to be short-lived, and after not new, but it’s only been feasible of new treatments,” she says. “To that there is a real possibility that in the past few years, thanks to understand all of the potential bene- they will have their disease controlled advances in biotechnology that allow fits of TIL therapy, it’s important to for a long time.” l immune cells that are harvested from include these patients in our studies.”

Garth Atchley with his wife, Judy, and his daughters, Jude (left) and Mary (right), on vacation in Wyoming in July 2017, just before he was diagnosed with cancer. Photo: Garth Atchley

16 | MSKNews Read more stories online: mskcc.org/summer-2021 | 17 Clinic Makes Life Easier Jacqueline found help at MSK’s Multi- disciplinary Bone Metastasis Clinic, established in 2019, where patients can Radiation Reimagined see all the specialists they need on the same day. How MSK Experts in Radiation Oncology Are Transforming Led by Dr. Yang, interventional radiologist Ernesto Santos, and orthope- Care for Metastatic Cancer dic surgeon Max Vaynrub, the clinic also includes specialists in rehabilitation medicine and management. With potent, knifelike beams that can effects and produces better outcomes. ‘I’ve Got This’ To help Jacqueline, the clinic team sear cancer cells yet spare healthy tissue, It’s used on about 8 percent of MSK MSK patient Tim Willis is a strong example. decided to use and stereo- there’s a growing arsenal of weapons patients now, but it’s expected to treat He came to Dr. Yamada in the fall of 2017 tactic body radiotherapy (SBRT) — the pioneered by Memorial Sloan Kettering’s 80 percent of them in the next decade, because cancer that started in his kidney same treatment used on the spinal radiation oncologists to reach tumors says Dr. Yamada. had spread, causing tumors on his spine. tumors of Tim Willis — which uses that have recurred deep inside delicate Tim was deeply worried about pain targeted, focused external beam radia- regions of the body. Higher Doses Also Mean and paralysis but remembers, “Once Dr. Tim Willis (left) and radiation oncologist Josh Yamada at an appointment in March 2021. tion to maximize the radiation dose to Radiation oncologist Josh Yamada Fewer Treatments Yamada gave me his medical assessment, the tumor while minimizing damage to and his colleagues are helping people “When we are able to deliver high doses he actually put his hand on my knee and opposite. The quality of life has been bone are about 100 times more common the normal tissue. Cryoablation involves with two particularly important advances of radiation safely within tumors, it is said, ‘Just so you know, I’ve got this,’ which absolutely outstanding.” than cancers that originate in the bone. inserting small needles into the bone developed at MSK: high-dose radiation actually a much more effective way to kill still gives me shivers.” They often cause acute pain and fractures metastases, freezing and killing the bits and computer software called ECHO. This tumor cells than giving small amounts of Six months later there was no evi- New Tech for Best Treatment and can be very frightening and disabling of tumor. algorithm exquisitely fine-tunes radiation radiation over an extended period of time,” dence of disease in Tim’s spine. “I reclaimed So far, about 1,000 spine tumors have been for patients already dealing with their doses, resulting in a level of precision that says Dr. Yamada. my life,” he says. “I feared being debilitated treated at MSK with the help of ECHO. primary cancer.” New Outlook Dr. Yamada says reduces possible side after this treatment. But it was the exact Creating this high-precision software took That was the situation facing “It’s unbelievable the difference it has seven years, with a team lead by MSK’s Jacqueline Hickey. She had repeatedly made,” says Jaqueline. “Now, I’m back to Linda Hong and Masoud Zarepisheh. fought off lung cancer since she was first sleeping, going out walking, and being Joseph Deasy, Chair of MSK’s Department diagnosed at age 40 in 2007. When the able to function and run a family.” of Medical Physics and Enid A. Haupt cancer returned in 2018, her personal phy- And she has a message for other Chair in Medical Oncology, compares the sician suggested Memorial Sloan Kettering. people with bone metastases. “There are technology to switching to a self-driving A combination of chemotherapy and so many new things coming out, and it’s “When we are able to car to navigate tricky paths. radiation helped. But eventually the cancer exciting — if one thing doesn’t work, deliver high doses of “ECHO is much more like an automated spread to her left rib. Jacqueline recalls, there’s always something else they can process that drives the car for you. The “It just hurt so bad, especially lying down try,” says Jacqueline. “Even with stage IV radiation safely within limitation with radiotherapy treatment up at night. I got so sleep deprived.” During lung cancer, I’m never giving up.” until now was that there was no way to tell the day, her activities were also severely Although Tim Willis recently needed tumors, that is actually that you actually had the best plan. ECHO hampered by pain. another round of treatment for more a much more effective gives us the best plan.” Jacqueline was leery of pain medica- spine tumors, he shares Jacqueline’s And because ECHO automates so much tions. As a mother of four, she explains, attitude. “When people hear that I’m a way to kill tumors cells of the planning process, Dr. Yamada be- “I want to be able to focus. I have one child stage IV patient,” he says, “they kind lieves it can help people far outside MSK. still at home and my firefighter husband of step back and say, ‘Oh, I’m sorry.’ And than giving small “In American hospitals, and especially in often has to work 24-hour shifts. I don’t I say, ‘No, I feel so much better than I amounts of radiation lower-resource countries, ECHO can reduce want to be conked out.” look on paper.’” l costs and allow medical teams with lower over an extended skill levels to give very precise radiation.”

period of time.” Life-Changing Pain Relief —Josh Yamada At MSK, new approaches to using can also relieve the physical Approximately pain that can make day-to-day living spine tumors have been treated uncomfortable and continuing therapy at MSK with the help of ECHO. more difficult — especially when cancer 1,000 spreads to the bones. That’s an area of intense focus for MSK radiation oncologist Jonathan Yang. He explains, “Cancers that spread to the

18 | MSKNews Read more stories online: mskcc.org/summer-2021 | 19 of the Department of Neurosurgery and metastases in the brain,” says neurosurgeon Moving Forward Theresa Feng Chair in Neurosurgery. Nelson Moss, the center’s surgical lead. In a three-hour procedure, Dr. Moss was Dr. Tabar helped establish a new Kathryn Beal, the tumor board’s able to remove all of the tumor. Susan Brain Metastasis Clinic that applies a lead radiation oncologist, recommended returned home the very next day. A few A New Frame of Mind highly efficient team approach for patients stereotactic radiosurgery for Susan. This weeks later, she had another round of like Susan. Experts from many fields study high-dose form of radiation was pioneered radiation to kill any lingering cancer a patient’s case and recommend next at MSK. Administered close to Susan’s cells. She has otherwise needed no MSK Experts Join Forces When Cancer Spreads to the Brain steps. To make the experience as easy as home at MSK Westchester, the radiation additional treatment and has regained possible, they organize appointments — shrunk each tumor, eliminating the activity function in her leg. She checks in with including radiation, if needed — to be done in two of them. Dr. Moss every three months. all in one day. This collaborative approach The third mass was about the size Susan is back at work, with her is also offered to patients whose primary of a walnut, in the part of the brain sunny attitude and sense of humor, A busy real estate broker and married oncologist is outside MSK. controlling perception and walking. It despite all she’s endured. When asked if mother of three, Susan van der Griend is was harder to treat and had started to she’d ever considered that melanoma an optimist by nature, used to making Great Minds affect her leg function. But Dr. Moss and could one day spread to her brain, she things happen and moving on. When she Like detectives mining a crime scene, MSK his colleagues came up with a surgical replied, “It didn’t even enter my head. was diagnosed with melanoma in 2017, specialists from neurosurgery, radiation plan. They also told Susan she could Well, I guess it did!” she decided to be treated near her home oncology, neuroradiology, medical oncology, choose to have the tumor monitored over Dr. Moss is optimistic about Susan’s in Connecticut. But a positive outlook physical therapy, and more pored over time. The decision was up to her. prognosis and hopeful for other patients didn’t stop the cancer. The disease Susan’s case in 2020. They discussed her “He was very balanced in his like her. recurred in four places. She went straight case at their Brain Metastasis Tumor Board, approach and clearly pointed out each “She and all our patients inspire to Memorial Sloan Kettering. a newly assembled group of specialists option. He wasn’t pushing me either way,” us to make brain metastasis a condition “There’s always somebody working who are focused on treating cancers that she recalls. “He said, ‘This is why I think that can be cured and ultimately on a new approach to cancer treatment spread to the brain. this is a good idea, but I can understand prevented,” says Dr. Moss. “We hope there,” says the 64-year-old. “She’s in a growing population of why you might want to wait.’ But I didn’t that MSK’s Brain Metastasis Clinic will Susan was given immunotherapy patients who have done incredibly well want the problem with my leg to persist bring us closer to that goal.” l under the care of MSK melanoma on cancer therapies but have tenacious or get worse.” medical oncologist Parisa Momtaz. Her cancer seemed to clear. But in 2020, a CT scan showed three new in her brain. “I felt betrayed by my body,” she recalls. “I thought, ‘How could this happen when the cancer had cleared up in the rest of my body?’ My glass is always half full, but this was a setback.” In the past, news like this was as- Viviane Tabar, who is the Theresa Feng Chair in Neurosurgery, helped found MSK’s new Brain Metastasis Clinic. sumed to be the beginning of the end for a patient. But MSK doctors are treating a blood test that can detect DNA from a metastatic brain cancer aggressively — brain tumor, her lab is also gaining new and getting good results. insight into how brain tumors evolve. “Our patients inspire us Having this precious DNA gives Storming the Fortress clinicians the ability to detect hundreds to make brain metastasis The brain is like a fortress, surrounded by a of genes that drive tumor growth. The goal a condition that can be barrier that protects it from dangerous is for doctors to determine the best pathogens. But that same barrier is also targeted therapy for a tumor without cured and ultimately what prevents cancer medicines from having to obtain a tissue biopsy from reaching their target. What’s more, cancer the brain. prevented. We hope that cells can sneak inside, like tiny Trojan These discoveries offer great promise MSK’s Brain Metastasis horses, by following the cells that are for future therapies, but there is also allowed into the brain. The cancer can also progress right now. Susan’s cancer has Clinic will bring us express molecules that latch onto the been kept in check by immunotherapy, brain’s gatekeeper — like talking their way radiation, and surgery. closer to that goal.” past security. —Nelson Moss But efforts are underway to find the Care for the Whole Person leaks in this barrier, says Adrienne Boire, “When a cancer spreads to the brain, it Susan van der Griend was stunned when physician-scientist in MSK’s Human creates enormous challenges, clinically melanoma recurred in her brain. But MSK’s Brain Oncology and Pathogenesis Program. and scientifically, but also psychologically Metastasis Tumor Board created a multifaceted plan that has kept Susan healthy. With the help of a liquid biopsy, which is for the patient,” says Viviane Tabar, Chair Photo: Susan van der Griend

20 | MSKNews Read more stories online: mskcc.org/summer-2021 | 21 Roz Kleban, a senior manager in the Department of Social Work and a 30-year veteran at MSK, helps lead both groups along with social worker Susan Glaser. Ms. Kleban explains, “Some people with metastatic breast cancer are afraid of Always by these groups because you might witness someone you get close to who is dying.” She continues, “But the people who participate see that as part of it. They think, ‘I need to be there for you because I know you’ll be there for me.’”

Your Side Turning Down the Radio How MSK Helps People Facing According to the American Cancer Society, more than 150,000 survivors of breast Metastatic Breast Cancer cancer are living with metastatic disease, which is far and away the most lethal form of breast cancer. Still, says Ms. Kleban, until 15 or 20 years ago, metastatic breast cancer was Ilene Thompson with her grandsons. Photo: Ilene Thompson “almost never mentioned, and a huge population of people was mostly ignored.” This distressed some patients with her breast cancer recurred and was diagnosed metastatic breast cancer at MSK, who at stage IV. started a group that raised awareness. After a career in healthcare, she “For many years,” says Ms. KIeban, “MSK recognized that she could use help, was the only facility that had support beyond her two grown daughters and a groups for people with metastatic “supportive group of friends in Brooklyn.” breast cancer.” She explains, “I knew the group members Today, one of the big aims of these would understand my issues. Sometimes MSK support groups is what Ms. Kleban calls family and friends just can’t, and I have to “turning down the radio.” She explains that explain the same thing over and over. That for people with metastatic breast cancer, can be frustrating and tiring.” “there’s a radio on in your head, 24/7, bang- In the support group, she says, “we ing at you about the illness, the treatments.” bounce off each other, and find out about She tells patients, “It’s the doctor’s new treatments and little home remedies job to keep the illness at bay. But it’s your to make yourself more comfortable.” There For Reilly Starr, the relationships inside her support job to keep that radio low. The volume is are also subgroups, including a writing always on, and sometimes it’s screaming, group and “one coming together that will do group are nearly impossible to describe — or for like when you’re waiting for the results of a meditation — these really help on a daily basis.” Roz Kleban tells patients it’s within their power to people outside to comprehend. “It’s hard to say scan.” But, she stresses, “it’s within your Just as important is the emotional live as well as possible. that these people are just friends,” she says. “The power to try to keep it as low as possible support. Ilene explains, “We have each part in the group. “We know many of us to live as well as possible.” other’s phone numbers and emails so we relationships are so deep. They are really like are living day to day, so we try to enjoy it. can just call if we want between meetings.” We encourage laughter and fun.” another treatment for your cancer.” A Godsend Before COVID-19, members also visited She concludes, “I’m really happy I Reilly is talking about the Metastatic Breast Cancer Support Group Ilene Thompson was looking to lower the those who had taken a turn for the worse. sought out this group. I know emotionally at Memorial Sloan Kettering. She joined after coming to MSK in 2019 volume when she came to MSK in 2018 after However, she stresses that joy also plays a seeking treatment for stage IV breast cancer that was diagnosed when this has been a godsend for me.” That’s a she was 40 years old. message echoed by Reilly, who says, “I’d Every other week, she joins a group of around eight to 12 people recommend this 1,000 percent. The group who are also facing metastatic breast cancer. Many have young children, More than is a necessity for me.” like Reilly, who has a 3-year-old. In this group, everything is on the table, Ms. Kleban says these women help says Reilly. “This is a safe place to cry and to share things your family and each other stay positive. While stopping friends don’t understand or can’t handle. It’s okay to be raw.” 150,000 survivors cancer’s spread does not depend on keep- The group is one of two at MSK. Reilly’s group focuses on the needs of breast cancer are living with metastatic disease. ing a positive attitude, having hope helps of younger people, who often are in the middle of careers and raising a patients find joy and human connection family. The other group is geared toward people facing metastatic every day. l breast cancer at a later stage in life. Reilly Starr (left) with her husband, Sean Mohammed, and their son. Photo: Courtney Bowles 22 | MSKNews Read more stories online: mskcc.org/summer-2021 | 23 MSKNews Inquiries about MSKNews should be addressed to: Memorial Sloan Kettering Marketing & Communications 1275 York Avenue New York, NY 10065 Phone: 212-639-3573 www.mskcc.org

CHIEF MARKETING & COMMUNICATIONS How Two Visionary OFFICER Roxanne Taylor Donors Are Changing EDITOR-IN-CHIEF Ami Schmitz SENIOR DIRECTOR, the Way Metastasis EDITORIAL Katie Sobolik Is Studied at MSK MANAGING EDITOR Andrew Roth CREATIVE DIRECTOR Alan Gerry has always recognized an opportunity when he sees one. Randi Press His parents both emigrated from Russia to New York City in their ART DIRECTOR youth so their families could build better lives. Kristin Glick By the time he was 12, Alan had built his first radio receiver. By the time he was 27, he had founded PHOTOGRAPHERS Liberty Video, which would become Cablevision Industries, the largest privately owned cable Rick DeWitt television company in the United States. His ambition to build a brighter future led him to Ethan Kavet Memorial Sloan Kettering. Karsten Moran In 2007, Alan and his wife, Sandra, met Joan Massagué of the Sloan Kettering Institute, one WRITERS of the world’s leading researchers in metastasis. “As soon as I heard Joan Massagué speak about Meredith Begley his work and goals for saving so many lives in the future through research, I knew we had to help Julie Grisham move the needle,” recalls Alan. Samantha Olson The results of that meeting revolutionized how metastasis is understood and treated, not just Bill Piersol at MSK but around the world. After Alan and Sandra gave their first gift in 2007, ten years of Jim Stallard unwavering support followed, and in 2017, the Alan and Sandra Gerry Metastasis and Tumor Matt Tontonoz Ecosystems Center was named in their honor. CONTRIBUTORS “The progress we’ve made at MSK has opened the door for massive discoveries in the coming Heather Graham decade,” says Dr. Massagué. “Alan and Sandra have helped create the current environment of optimism, and they are essential partners in this work.” Read more about how Alan and Sandra Gerry’s support is helping transform our understanding NCI-designated Comprehensive Cancer Center ©2021 and treatment of metastasis at the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center at mskcc.org/summer-2021. l

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