Breakthroughs Magazine 2024

breakthroughs

YALE CANCER CENTER AND SMILOW CANCER HOSPITAL LEADERSHIP

Yale Cancer Center

DIRECTOR

Eric P. Winer, MD

DEPUTY DIRECTORS

Daniel DiMaio, MD, PhD, Laboratory Science

Roy Herbst, MD, PhD, Clinical Affairs

Melinda Irwin, PhD, MPH, Population Sciences

ASSOCIATE DIRECTORS

Barbara Burtness, MD, Translational Sciences

Ian Krop, MD, PhD, Clinical Sciences

Harriet Kluger, MD, Education, Training & Faculty Development

Megan King, PhD, Basic Science

Patricia LoRusso, DO, Experimental Therapeutics

David F. Stern, PhD, Shared Resources

Marcella Nunez-Smith, MD, MHS, Community Outreach & Engagement

Faye Rogers, PhD, Diversity, Equity & Inclusion

CLINICAL RESEARCH

Ian Krop, MD, PhD, Associate Director, Clinical Science

Alyssa Gateman, Executive Director, Clinical Trials Office

DIRECTOR’S COUNCIL

Louis Chenevert, Chair

Roslyn Meyers, Co-Chair

Smilow Cancer Hospital

PRESIDENT AND PHYSICIAN-IN-CHIEF

Eric P. Winer, MD

SENIOR VICE PRESIDENT AND EXECUTIVE DIRECTOR

Lori Pickens, MHA

VICE PRESIDENT, NETWORK SERVICES

Elizabeth Herbert

CHIEF MEDICAL OFFICER

Kevin G. Billingsley, MD, MBA, FACS

INTERIM VICE PRESIDENT, PATIENT SERVICES

Tracy Carafenno, RN, MS

CHIEF QUALITY OFFICER

Scott Huntington, MD, MPH, MSc

CHIEF HEALTH EQUITY OFFICER

Marcella Nunez-Smith, MD, MHS

DEPUTY CHIEF MEDICAL OFFICER SURGICAL SERVICES

Mehra Golshan, MD, MBA, FACS

CHIEF NETWORK OFFICER AND ASSOCIATE CHIEF MEDICAL OFFICER

Jeremy Kortmansky, MD

CHIEF AMBULATORY OFFICER

Sarah Shellhorn, MD

CHIEF PATIENT EXPERIENCE OFFICER

Tara B. Sanft, MD

DEPUTY CHIEF MEDICAL OFFICER

THERAPEUTIC RADIOLOGY

Lynn Wilson, MD, MPH, FASTRO

EXECUTIVE DIRECTOR, ADMINISTRATION

Sonia Grizzle

YCC Research Programs

CANCER IMMUNOLOGY

Marcus Bosenberg, MD, PhD

Mario Sznol, MD

Carla Rothin, PhD

CANCER PREVENTION AND CONTROL

Xiaomei Ma, PhD

Michaela Dinan, PhD

CANCER SIGNALING NETWORKS

Katerina Politi, PhD

Don Nguyen, PhD

Isaac Kim, MD, PhD, MBA

DEVELOPMENTAL THERAPEUTICS

Karen Anderson, PhD

Barbara Burtness, MD

GENOMICS, GENETICS, AND EPIGENTICS

Lajos Pusztai, MD, DPhil

Jeffrey Townsend, PhD

Qin Yan, PhD

RADIOBIOLOGY AND GENOME INTEGRITY

Joseph Contessa, MD, PhD

Megan King, PhD

YCC Transdisciplinary Centers

CENTER FOR MOLECULAR AND CELLULAR ONCOLOGY Director, Markus Müschen MD. PhD

CANCER OUTCOMES, PUBLIC POLICY, AND EFFECTIVENESS RESEARCH

Director, Cary Gross, MD

YALE CANCER BIOLOGY INITIATIVE Director, Mark Lemmon, PhD

YALE CENTER FOR IMMUNO-ONCOLOGY Director, Marcus Bosenberg, MD, PhD

DIRECTOR’S MESSAGE

We hear often that healthcare is broken, but not enough about what is being done to make it better. The views are varied and depend on who is answering the question. But for many clinicians, who are often under huge pressure to see more and more patients in the day, there is a desire to step back, slow the pace, and focus on the patient. Indeed, the patient is at the center of all that we do. We need to embrace patients as our partners, as an integral part of the healthcare team. When an oncologist enters a room with a patient, there is an opportunity to open a door and walk into a patient’s life in a way that is true of few other fields.

Cancers vary greatly from one to another and so do individuals. Decisions about treatment approaches must be personalized, and need to reflect the patient’s particular cancer, their other health problems, social circumstances, unique set of preferences, goals, and so much more. When patients and their family members are fully involved in treatment decisions and care, the medical outcomes are better, side effects from treatment are diminished, and patients are more satisfied with their experience. Building partnerships between patients and clinicians must begin early in the relationship, and it may take time to build trust. In the end, a true partnership will lead to better care, and will also enhance our ability to conduct clinical trials, answer key scientific questions, and ultimately make cancer care better in the future.

As we consider patient-clinician partnerships, it is imperative that we emphasize the challenges faced by the many individuals at risk for cancer care disparities, including patients who are from underrepresented racial and ethnic groups, patients living in poverty, patients who may not have had extensive formal education, patients from the LGBTQ+ community, those with mental health challenges, and so many others. For many of these individuals, partnerships with physicians may be even more difficult to form, but are absolutely indispensable if we are to mitigate inequities in cancer care.

Our overarching goals at the Yale Cancer Center and Smilow Cancer Hospital are to provide the best cancer care that is available today and ensure that our treatments will improve in the future. We are committed to care, research, and education. And we are determined that everyone with cancer who walks through our doors or lives in our community has equal access to cancer care and to the advances provided by research.

Sincerely,

Eric P. Winer, MD Director, Yale Cancer Center; President and Physician-in-chief Smilow Cancer Hospital

DELIVERING THE BEST CARE

The Promise of Partnership Realized

By Naedine Joy Hazell

When a patient arrives at Smilow Cancer Center they are assured of a clinical team drawn from an experienced and deep bench, a multi-disciplinary team that can deliver stateof-the-art care and partner with the patient and their family. It includes highly trained cancer specialists, informed by breakthroughs from Yale’s diverse research programs and from centers around the world. The goal is delivery of cutting-edge care with understanding and compassion.

Briefly put, the partnership of Yale Cancer Center and Smilow Cancer Hospital is a nimble matrix with a multi-faceted focus on individuals with cancer.

“As we deliver the best care available today, the clinical team knows that we must do even better in the future. With that goal in mind, we are also conducting research in the laboratories and in the clinic to develop the next generation of cancer therapies. But we cannot do research in a vacuum.

“Now, more than ever before, we need to reach out to our patients, the broad patient community, and the general public, to understand what we need to prioritize, and we need to listen to their guidance.”

Eric P. Winer, MD

We need to listen to our patients about what is missing and what they need,” said Eric P. Winer, MD, who leads the YCC/Smilow partnership as director of YCC and president and physician-in-chief of Smilow.

Nearly half of Connecticut residents with cancer are seen at one of the 16 Smilow sites, 15 of which are in the state and one in Rhode Island. The creation of so many points of care illustrates a concerted commitment to patients first, a recognition of the value in closer-to-home medicine.

Staffing and services at many Smilow cancer sites of care have expanded in recent years. Each site is increasingly staffed by oncologists who specialize in specific malignancies. For example, patients with breast cancer see breast cancer oncologists and those with colon cancer see oncologists who specialize in gastrointestinal malignancies. Clinical trials are also available at every site of care, so patients do not need to come to New Haven to participate in most research studies.

“The seamless partnership of Smilow and the Yale Cancer Center ultimately enables us to align and integrate all cancer specialties with a full complement of wrap-around services delivered through all cancer disciplines,” said Lori Pickens, MHA, senior vice president of cancer services and executive director of the Smilow Cancer Hospital. “[They] include, but are not limited to, doctors, researchers, educators, nurses, social workers, genetic counselors, pharmacists, all collectively engaged in patient care, clinical trials, survivorship

and if needed, end of life comfort care.”

YCC/Smilow’s intentional expansion into 15 towns and cities outside of New Haven was influenced by input from patients and families, as well as community leaders.

Every individual with cancer faces a range of struggles. Programs or support services that lessen or eliminate some of the challenges may also address contributors to inequitable healthcare. Studies of disparities in cancer outcomes suggest that these outcomes can be improved through navigation that addresses issues such as transportation, insurance, work schedules, and childcare responsibilities.

The YCC multi-faceted approach to cancer includes substantial resources devoted to prevention and education. For example, hundreds of Connecticut residents and beyond have participated in YCC studies focused on nutrition, physical activity, and tobacco use—information that is important for cancer prevention and survivorship research. That data helps inform public-facing educational efforts designed to stop cancer before it starts, explained Melinda Irwin, PhD, MPH, Susan Dwight Bliss Professor of Epidemiology (chronic diseases) at Yale School of Medicine. She is also YCC deputy director, Population Sciences.

“And a new focus of our attention is on people diagnosed with cancer at younger ages, as well,” said Dr. Irwin. She added that the breadth of YCC published research is essential to augmenting overall public and academic knowledge about cancer, possible causes, and what works as effective education to help prevent it.

“Working closely with Yale Cancer Center’s community outreach and engagement program and the community advisory board, we are tackling cancers common or rising in Connecticut,” Dr. Irwin said.

YCC’s Center for Community Engagement and Health Equity (CEHE) was created to bring a concerted focus to health equity and improving cancer patient outcomes, with an emphasis on historically underserved neighborhoods.

“Now, more than ever before, we need to reach out to our patients, the broad patient community, and the general public, to understand what we need to prioritize,” Dr. Winer said. “And we need to listen to their guidance.”

In operation for four years, CEHE already considers 140 community organizations to be partners in outreach and education, helping with initiatives including cancer screening events. Some $360,000 has been earmarked by YCC for community grantmaking through 2027. Last year, YCC made three $10,000 awards to community organizations to conduct their own research.

“It is essential to YCC that we involve our community members in the work we do. To expand this effort we are thrilled to provide pilot grants to three local community organizations doing important work related to cancer screening, research, and care,” Dr. Winer said in announcing the grants. They went to the Community Action Agency of New Haven, Inc., for informational campaigns, workshops, and community events to raise awareness about different types of cancer,

risk factors, and ways to lead a healthier lifestyle; the Bridgeport-based Sister Girl Foundation that provides awareness, education, support, and advocacy to women with endometriosis, breast and ovarian cancers; and Sisters’ Journey, a support group for breast cancer survivors and their families and friends.

CEHE coordinates with YCC’s Diversity, Equity, and Inclusion (DEI) effort and Cancer Research Training & Education Coordination (CRTEC). Leaders of the three programs work closely together to maintain the pipeline of future cancer researchers, scientists, and clinicians through educational outreach that extends from area high schools to post-doctoral programs. The goal is to foster a diverse new generation to be at patient bedsides and in the research labs.

“Our goal is to expand our pathway programs in collaboration with CRTEC to reach students throughout their academic journey,” said Faye Rogers, PhD, associate director for DEI at the cancer center and associate professor of Therapeutic Radiology at Yale School of Medicine. “For example, we recently received funding to support the creation of an American Cancer Society (ACS) Diversity in Cancer Research Postbac Fellows Program. In collaboration with CRTEC the students will participate in the Cancer Biology Training Program.”

TREATMENTS FOR TODAY AND TOMORROW

Medicine and research have enjoyed a

“The essential partnership of Smilow and the Yale Cancer Center ultimately enables us to align and integrate all cancer specialties with a full complement of wrap-around services delivered through all cancer disciplines.”

Lori Pickens, MHA

collaborative relationship since New Haven became home to Yale School of Medicine as well as a state hospital in the early 1800s. Since the 1840s, Yale School of Medicine students have written a thesis based on original research, reinforcing the message of its importance institution wide.

Research could easily get lost in the immediate concerns and urgency of the day-to-day at Smilow. But research, and its tremendous promise, remain a crucial priority for virtually all of the oncology clinicians. Research is how cancer treatment will be better in 2030 than it is in 2023. Within YCC, researchers are divided into distinct programs and at any time there are hundreds of research projects underway, including clinical trials, laboratory experiments, and studies that look at large populations.

“The basic science laboratories at the Yale Cancer Center continue to make important discoveries that shed important new light into the underlying causes of cancer,” said Daniel DiMaio, MD, PhD, who is deputy director, Laboratory Science at YCC and Waldemar Von Zedtwitz Professor of Genetics, professor of molecular biophysics and biochemistry, and of therapeutic radiology at Yale School of Medicine (YSM).

Dr. DiMaio specifically noted work related to the role some chromosomal abnormalities play in cancer growth and another study of mechanisms that tissues use to limit the growth of mutated cells, which could form cancer cells. The chromosomal study was published in Science magazine by a team led Jason Sheltzer, PhD, assistant professor of Surgery (oncology) and of Genetics, YSM. The paper on tissue mechanisms was published in Nature, by the YCC lab of Valentina Greco, PhD, who is Carolyn Walch Slayman Professor of Genetics at YSM.

“These sorts of basic science findings are required for us to understand the fundamental mechanisms that lead to cancer, and they point the

way toward novel approaches to prevent or treat this disease,” Dr. DiMaio said. Scientists in the research programs—Cancer Immunology, Cancer Prevention & Control, Developmental Therapeutics, Cancer Signaling Networks, Radiobiology & Genome Integrity and Genomics, Genetics and Epigenetics—seek partners and collaborators throughout Yale and beyond, including other public, and private, research institutions in the US and around the world.

ADVANCING THE SCIENCE TO CRITICAL LAST STEPS

Of the many steps in research, approval for clinical trials follows extensive preclinical work. Treatments that are most promising after those initial tests are developed into clinical trials. All of today’s most advanced cancer treatments followed similar paths to final approval from the US Food & Drug Administration.

The clinical trial portion of the journey from idea to useful treatment can be the most personneland time-intensive, given the primary goal of safety for participants as well as data collection. Treatment on a clinical trial requires attention to detail because the team is simultaneously trying to provide the best patient care and learn how to improve care in the future. Ultimately, new drugs only become a standard approach after FDA approval.

The National Cancer Institute has, for some years, promoted efforts to diversify clinical trial participants in terms of race, ethnicity, gender, age, and individuals from historically underrepresented regions of the US. More diversity is linked to greater confidence in results, allaying fears that a treatment might not be effective, or safe, for a group of patients and it could further widen disparities in cancer treatment outcomes.

A national study presented in September at the Conference on the Science of Cancer Health

Disparities in Racial/Ethnic Minorities and the Medically Underserved—sponsored by the American Association of Cancer Researchers— found that trial diversity had grown from the period 2000-2003 to 2020-2022.

YCC’s clinical trial office is supporting the Early Phase Clinical Trial Hybrid Decentralization Project, identifying, and removing barriers to participation in first-phase clinical trials. This project, spearheaded by Drs Patricia LoRusso and Marcella Nunez-Smith, is well funded from both industry partners and foundations. It will allow Yale to recruit early-phase trial participants from

SEEKING INPUT

The Community Advisory Board

across the state, and one of the specific goals is to increase the diversity of the trial participants.

“Today’s clinical trials are tomorrow’s standard of care,” said Roy Herbst, MD, PhD, Ensign Professor of Medicine (medical oncology) and professor of pharmacology at YSM; deputy director, YCC; and chief of medical oncology, YCC and Smilow Cancer Hospital. “By ensuring all patients have access to the most scientifically driven studies we ensure a patient gets the best possible standard of care with the opportunity to reach even farther to raise the bar with new science from Yale and elsewhere.” •

The board gives voice to the community. It includes about 20 people from community-based organizations across Connecticut. The CAB meets monthly; quarterly meetings are planned with the YCC director and Smilow president this year. In the past two years, the CAB members have discussed projects with 14 YCC members and their research teams.

The Internal Advisory Board

The board provides guidance on overall YCC strategy with a focus on how best to optimize the use of Yale institutional resources and foster further collaborations across the university. The IAB has eight senior university leaders with broad expertise and five members from the community board. The IAB meets annually and as necessary to provide guidance on a variety of topics.

The External Scientific Advisory Board

The ESAB’s 18 members include several cancer center directors, who provide senior-level advice on the progress and direction of YCC. ESAB meets annually and as needed. Its critiques of specific programs have driven improvement and investment. Its recommendations are carefully considered and frequently implemented.

The Director’s Council

The council includes 20 donors at present and is likely to grow. The council raises philanthropic support for YCC to advance strategic priorities and members also offer advice and organizational questions. The assistant vice president for cancer philanthropy will be working closely with the council.

Connecting Medicine... ...and Biology

WELL BEYOND BASIC: YOUNG MULTIDISCIPLINARY CENTER MAKING STRIDES

By Emily Montemerlo

The term “basic” is used to describe scientific discoveries made on a fundamental level. They are essential to translational work by scientists and physicianscientists, who bridge cancer biology and clinical investigation, specifically to bring better treatments and diagnostic tools to patients.

It’s been an exciting year for basic science research at the Center for Molecular and Cellular Oncology (CMCO), says its inaugural director Markus Müschen, MD, PhD, Arthur H. and Isabel Bunker Professor of Hematology at Yale School of Medicine

“Three of our faculty received their first federal grants and another one is currently under submission, which is a huge milestone and recognition of their impactful work. We currently have a lot of exciting research underway that could

“Our

center aims to support our faculty by creating an

institutional infrastructure to help our junior research groups grow and build a long-term career. We do this by creating a community on multiple levels….Mentorship is a very important part of what we do.”

Markus Müschen, MD, PhD

potentially benefit many patients, and our external research funding doubled over the last year, which is quite amazing,” Dr. Müschen said of the CMCO, which is one of four transdisciplinary centers at Yale Cancer Center (YCC).

Dr. Müschen joined Yale in 2020 and has grown the program to six core members and counting, along with numerous students, postdocs, and faculty mentees.

“Our center aims to support our faculty by creating an institutional infrastructure to help our junior research groups grow and build a longterm career,” Dr. Müschen said. “We do this by creating a community on multiple levels. We are fortunate to have contiguous lab space where our six resident physicians can interact not only with each other, but with other members of the center as well, including senior and junior faculty and our physician-scientists. Mentorship is a very important part of what we do.”

The commitment to infrastructure and mentorship explains the decision to build “the aquarium,” a special space in the middle of the CMCO.

At one of the monthly faculty lunches where the lab members share ideas and thoughts on current projects, there was a realization that research increasingly was becoming computational, but the center’s physician-scientists were not adequately trained to mentor their computational science trainees.

“These trainees are performing important work

to support a diverse research portfolio, but most were working remotely due to the need for a dry bench space, and as a result, felt disconnected from the other lab members,” explained Dr. Müschen.

“To fix this, we underwent a building project in the middle of the lab to create a dry bench space termed ‘the aquarium.’ This allowed our trainees to be in the middle of the lab with glass around them, and to form their own group to help mentor each other. This not only created a forum where students and post-docs could interact, but it also makes us more attractive for the recruitment of future computational biologists,” Dr. Müschen said.

The computational science trainees work in each of the CMCO labs including that of Dr. Müschen (leukemia and lymphoma), David Braun, MD, PhD (kidney cancer), Jeffrey Ishizuka, MD, DPhil (melanoma), and Frederick Wilson, MD, PhD (lung cancer). The labs aim to meet the center’s overall goals to provide a home for both basic and translational research, particularly for groups that are led by physician-scientists, and to assist them on what can often be a difficult career path leading both a research group and staying active in the clinic.

Members of the CMCO hold primary appointments in medical oncology or hematology at YCC and participate in one or more YCC Clinical Research Teams (CRTs) and YCC research programs relevant to their laboratory research and clinical interests, promoting a collaborative environment for the better understanding of cancer

biology. They are critical to YCC’s commitment to translational science.

As for the future, more growth is planned. Dr. Müschen said he is particularly excited about investing more focus in training clinical fellows in partnership with Yale Medical OncologyHematology Fellowship Director, Alfred Lee, MD, PhD. He also foresees more connections with physicians who are primarily in the clinic, as opposed to the physician-scientists who divide their time between the lab (80 percent) and the clinic (20 percent).

Another exciting area of focus will be maximizing the potential of treatments that are already FDA approved and being used in the clinic. For example, the CMCO has already repurposed a class of drugs used for a variety of reasons, to focus solely on blood cancer. There is also hope for

CENTERS OF ATTENTION

a multicenter clinical trial run by Shalin Kothari, MD, a YSM assistant professor of medicine (Hematology), to show that patients with blood cancer who are not currently receiving these drugs, can benefit from their use. Dr. Müschen’s personal research includes understanding B-cell signaling mechanisms and how these mechanisms contribute to malignant transformation and development of drug-resistant leukemia and lymphoma. While the growth of the CMCO has been significant and the research fast-paced, both the sense of community and the success of the researchers remain top priorities. The environment of mentorship and inclusivity helps build connections and provides cohesion amongst the center’s many members, but most importantly, it makes significant contributions possible that will one day soon benefit all patients. •

CMCO is one of four transdisciplinary centers that enhance the activities in YCC. Center leaders are all members of the Director’s Cabinet. The centers bring in institutional resources and recruits, span the six Research Programs, and provide opportunities for training. A large majority of faculty in the Centers are also members of YCC. The other three centers are:

Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER)

LEADER, CARY GROSS, MD

The center is comprised of researchers and clinicians from across the Yale School of Medicine (Therapeutic Radiology, Surgical Oncology, Hematology/Medical Oncology, OB/GYN, Urology, and Internal Medicine) and Public Health (Epidemiology and Health Policy). It also provides training and mentorship to the next generation of cancer policy and outcomes researchers.

Yale Cancer Biology Institute (YCBI)

LEADER, MARK LEMMON, PHD

The institute connects scientists from across Yale to study the common underlying causes of cancer, wherever it appears, and seeks to understand core cellular and molecular links across multiple cancers.

Yale Center for Immuno-Oncology (YCIO)

LEADER, MARCUS BOSENBERG, MD, PHD

The center is a partnership between Yale Cancer Center and the Department of Immunobiology at YSM. It was established in 2018 to build on YCC’s leadership in immunology, immunobiology, and the development of innovative cancer immunotherapies.

FROM IDEA TO INTERVENTION

Treatments Found in Translation

Behind every cancer patient stands a long line of researchers they will never know, although their work and expertise remain critical to their outcomes.

Reflecting the complexities of the disease, cancer research is an ever-evolving field requiring constant infusions of innovation and funding. Starting this year, those resources at Yale Cancer Center will be augmented by its Translational Incubator, an initiative to further support and accelerate cooperation and collaboration among Yale experts.

“There’s basic science research that we want to get to patients, and we just have to create more connections to move it forward,” explained Barbara Burtness, MD, associate director for translational research at Yale Cancer Center and co-leader of the Developmental Therapeutics research program. “The purpose of the incubator

[is to] take the culture of translation to all our scientists and all our clinical investigators.”

In the research world, “translation” means transforming basic scientific findings in a laboratory setting into potential treatments for disease. It routinely involves painstaking research to provide evidence of its viability as a treatment. Once that phase is complete, approval is sought to test the potential treatment with patients who volunteer for clinical trials.

Sometimes referred to as “bench to bedside,” the translational process is closely regulated and typically takes years. Facilitating this process is the aim of the Translational Incubator.

“Our purpose is to create excitement among

potential users…all the people who have not consistently been seeking out translational opportunities,” said Dr. Burtness, the Anthony N. Brady Professor of Medicine (medical oncology) at Yale School of Medicine.

It’s “how we can jump-start the next step. You have to get the right people into the room,” she said. “You have to figure out who should be talking to each other and then create [ways] they can do that.”

Like tech, business, or development incubators, the Translational Incubator is meant to provide evaluation, guidance, and assistance to investigators who believe that a finding in the laboratory is ready to be explored clinically or a clinical finding merits laboratory investigation.

The incubator will be “a touchpoint for people as they want to think about accessing shared resources, and we’ll be keeping a curated list of translational funding opportunities,” Dr. Burtness said.

In addition, the incubator will direct investigators to the cancer center shared resources, which include services, technologies, and scientific consultations in a half dozen areas that include cancer biostatistics, pathology tissue services, genomic analysis, and molecular discovery. Each resource is led by a cancer center expert.

The incubator also will have its own resources, including a science writer as well as a research affairs professional, who will have office hours to meet with researchers. Pratima Chaurasia, PhD,

is enthused about that new role. “I’ve dedicated my life to science,” said Chaurasia, a successful scientist who has just completed a new assay in the Yale Center for Genome Analysis. “I’m excited about helping with building [relationships]…about helping them to build a network and the right collaborators…so they can develop their scientific ideas and careers.”

The incubator’s steering committee, chaired by Dr. Burtness, will include five YCC associate directors—Translational, Clinical, and Basic Sciences, Shared Resources and Experimental Therapeutics—and the deputy director, Population Sciences. It will meet monthly to consider concepts from basic and clinical investigators and to prioritize the proposals, based in part on catchment area needs, alignment with the center’s strategic priorities, and potential impact. The steering committee will also meet bimonthly with the cancer center’s six research program leaders to promote collaboration and bring concepts to the Incubator.

“We’ll also keep track of publications and grant submissions,” so that the information can be shared and suggest areas for partnerships, Dr. Burtness said. “It could be like ‘Have you seen so-and-so’s amazing data? We are thinking about how cool this would be in your model.’ It’s trying to understand where the synergies might be.”

Those multidisciplinary synergies, or “team

“There’s basic science research that we want to get to patients, and we just have to create more connections to move it forward. The purpose of the incubator [is to] take the culture of translation to all our scientists and all our clinical investigators.”

Barbara Burtness, MD

science” collaborations, leverage the strengths and expertise of diverse professionals in different aspects of the same field and can be effective in tackling complex scientific and societal problems, says the National Cancer Institute. Team science is important to nurture as competition for research dollars intensifies, despite the enviable fact that the US government devotes more money to cancer research, about $7.3 billion in 2023, than any other single entity in the world.

The Translational Incubator’s precursor was the less formal Drug Candidate Review Group operated by the leaders of Developmental Therapeutics (Dr. Burtness and Karen Anderson, PhD, YSM professor of pharmacology and of molecular biophysics and biochemistry) over the last six to seven years. The review group provided a forum where colleagues could learn about “this large number of promising new compounds [with the aim of] connecting those people with others doing disease-specific research, disease-specific models and [who were] interested in taking these into the clinic,” Dr. Burtness said.

interactive, every slide got discussed” and ideas were kicked around.

Among the translational projects advanced by YCC and the Drug Candidate Review Group are pH low insertion peptides, combination FGFR and HDAC inhibitor therapy, and KDM5 inhibitors. Those research discoveries, combined with efforts to translate the work into viable treatments via Developmental Therapeutics, has yielded other outstanding Yale successes, including:

• The proteasome inhibitor molecule carfilzomib, now FDA-approved as standard of care for multiple myeloma

• Development of proteolysis-targeting chimeras (PROTACs) with applications envisioned for numerous cancers and the advancement of the PROTAC ARV-110 for treatment of metastatic castrate-resistant prostate cancer (mCRPC) in a clinical trial at Yale.

“With the launch of the Translational Incubator, we believe the process of moving concepts from the lab to the clinic will be more streamlined than ever before,” said Eric Winer, MD, the director of YCC.

“The idea was how could we help these people who had incredible basic science stories find translational ways forward,” Dr. Burtness said of the review board. It met about a half dozen times a year, assembling different experts depending on the science being reviewed, but with a handful of core members who attended each session.

“We assembled a small group of translational investigators, animal modelers, pathologists interested in biomarker characterization, and early phase clinical trialists,” she explained. “It was very

Treatment-altering cancer research at Yale stretches back to the earliest chemotherapy, first introduced for patient use at Yale in the early 1940s, and remains robust today, now newly supported by the Translational Incubator.

Not every Yale researcher will be physically present at a patient’s bedside, but their work makes each step in their cancer treatment possible.

— Naedine Joy Hazell

CRITICAL FINAL STEPS IN DEVELOPING NEW TREATMENTS

Honing the Focus of Clinical Trials

The halls of Yale Cancer Center rarely ring with anything other than footsteps, hurried hellos, and the occasional polite mention that a meeting has let out and there are leftover bagels in the kitchenette.

The action takes place in 16 Smilow Cancer Hospital locations, the labs, and the research programs.

But on some days, Patricia M. LoRusso, DO, PhD(h), professor of Medicine (Medical Oncology), Yale School of Medicine, chief of the Early Therapeutics Program, and associate cancer center director for Experimental Therapeutics is in her YCC office and she brings a unique energy.

“Hey, how you doing? Yeah, it’s been a while,” Dr. LoRusso says, smiling into her phone. She is behind her office desk with the door open, but it is as if she is beside whomever is on the other end of the phone. “Hey listen, I’m calling about…yeah, that trial. Is there any way we can fit one more? I’ve got this patient, just saw her today….”

Dr. LoRusso’s heart is always in clinic. And when she’s not physically there, it seems she’s talking about clinic, or bargaining to improve support of patients in clinical trials, or advising why there should be more or greater access to clinical trials.

Clinical trials are among the critical final steps in bringing a new treatment to patients and they typically follow years of earlier research, modeling using mice, other preclinical model systems and published findings. Successful clinical trials with patients are necessary to obtain federal approval for a treatment’s wider use. Dr. LoRusso’s message about the importance of clinical trials is similar

whether she is talking to a patient or is in an advisory meeting at the White House, as she was a few months ago, or part of a panel at the annual “People v. Cancer” symposium hosted by the national magazine, The Atlantic. “Less than 3% of [cancer] patients are going on clinical trials and the numbers are declining,” Dr. LoRusso told The Atlantic audience in November.

As potential drug treatments become increasingly

focused, the need for more trials is critical and they need to include more diverse patients. “There was a publication last year in JAMA that showed that up to 40% of clinical trials had no underrepresented patients. It’s important to have representation of these populations because we have to understand, before these drugs become FDA-approved for commercial use, how these drugs are going to act in all patients” in terms of benefits and toxicities.

“As we become more knowledgeable, we realize the many different faces and diseases of cancer. Each patient, even with a similar diagnosis, has a different disease. We are not at the level of personalization yet that I think we need to be to have the greatest impact.”

Patricia M. LoRusso, DO, PhD(h)

An internationally recognized expert in drug development and early-phase clinical investigation of novel therapies, Dr. LoRusso has always done clinical research.

At present, YCC has 26 actively enrolling phase 1 trials, and Dr. LoRusso and team are working to increase accessibility and participation. The intent is to improve education tools, including “myth busting” messaging about trials on monitors in Smilow clinics; continued coordination with the Center for Community Engagement and Health Equity and less cumbersome informed consent forms. In addition to recruiting additional faculty, as the early phase program is growing along with the excitement in the novel drug therapy landscape, Dr. LoRusso hopes to recruit 250 patients to early phase trials of novel therapies in 2024 and to expand efforts beyond the Smilow site in Bridgeport/Trumbull.

It’s a heavy lift for 2024 given that, in April, Dr. LoRusso became president of AACR—the American Association of Cancer Research—the largest cancer research program internationally, with a membership of 58,000. But the pull of her patients will remain.

“I love what I do,” she said. “It humbles you. It makes one realize how blessed we are to be healthy, and how very much of a hero each of our patients are, for helping to advance new treatments.

“You’ve got to remember that the patients, for the most part, have advanced disease…many of them have no other options. They are the heroes.

They are giving so much time, of what little time they have left. They go on trials in the hopes that they respond to the new therapies, often having failed all standard drugs that are typically given to patients with their disease. They are hoping that participation will allow them to live longer, but they also are helping to develop new drugs for mankind,” Dr. LoRusso said.

Dr. LoRusso uses the word “phenomenal” to describe the leap forward in cancer research enabled by the groundbreaking work on the human genome, new lab technologies, and computational advancements. The drugs being developed are more selective for specific targets and tumor types, meaning they benefit thinner slices of the cancer patient population, but bring the potential for more targeted treatment. Hopefully, all this translates to a greater response and a longer life.

As for the always hopeful prediction that a cancer cure is closer every day, Dr. LoRusso allows that “We know a lot, but I don’t think we are there. We are closer, but we’re not on the cusp — we have quite a long way to go.”

“As we become more knowledgeable, we realize the many different faces and diseases of cancer. Each patient, even with a similar diagnosis, has a different disease. We are not at the level of personalization yet that I think we need to be to have the greatest impact,” she said.

“That’s going to come with more translational research, more bedside to bench research, more

clinical research in terms of novel treatments, designs and approaches to giving drugs—which I think is hopefully going to translate to better individualized therapies for patients,” she said, emphasizing the importance of the process being bi-directional—from lab bench to clinical bedside and then back to the bench.

Still, Dr. LoRusso is quick to note the impressive advances and she’s seen many since she began. Her career in cancer research can be described as beginning before she even graduated high school. That was when she lost both parents to cancer in her youth.

“I always look at cancer as my enemy. It’s been my enemy for many, many years. When my parents

were sick, there were no drugs,” she told an AACR interviewer in a video produced in 2022. The video was made when she won the prestigious Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research.

“For clinical research, your greatest resource is the patients — the most precious, valuable resources,” she said.

So, while the quest for cures continues, breakthrough treatments that sabotage or frustrate cancer’s return or its growth still translate to lives saved and years lived. “That’s the fuel that has kept me going,” Dr. LoRusso said. •

TYPES OF CLINICAL TRIALS

Clinical trials can be designed to address different research questions and can provide answers to multiple questions. For example, treatment trials designed to primarily determine clinical outcomes, such as the efficacy of an anticancer drug, can also evaluate the impact of the treatment on quality of life. Cancer clinical trials include:

Prevention trials are designed to learn whether people without a cancer diagnosis can reduce their risk of cancer by proactively taking certain actions, such as increasing physical activity and eating healthily.

Screening trials seek to evaluate new tests to detect cancer before symptoms arise, with the goal of determining whether the screening test will reduce deaths from cancer.

Diagnostic trials are designed to test new ways to diagnose a certain type of cancer.

Treatment trials are designed to determine whether new treatments or new ways of using existing treatments—alone or in combinations—are safe for patients and effective in treating cancer.

Quality of life trials examine whether patients with cancer can improve their quality of life by taking certain actions, such as attending support groups or exercising more. These trials are also known as supportive care or palliative care trials, and many evaluate the effects of certain cancer medications and treatments on quality of life.

Natural history or observational trials are used to learn more about how cancer develops and progresses by following patients with cancer or individuals who are at high risk for developing cancer over a period of years.

Correlative studies are designed to examine the usefulness of a candidate anticancer drug by using biomarkers, such as proteins, as indicators of the desired clinical outcome when the effects of the drug on key clinical outcomes, such as reduction in tumor size, may not be apparent.

Source: AACR CANCER PROGRESS REPORT 2023

— Naedine Joy Hazell

FURTHER FOCUS ON YCC AND SMILOW PRIORITIES

Confronting Contrasts, Inequities in Care

Tracy Battaglia, MD, MPH, is the first leader of the new Initiative to Address Cancer Inequities at YCC and while it might be a bit early to discuss specifics, she could not be more poised to tackle the pervasive issues in Connecticut.

After a prestigious career at Boston University (BU) and Boston Medical Center, the largest “safety net” medical center in New England, Dr. Battaglia says she is “very fortunate to build off of the strengths that already exist at the Yale Cancer Center, particularly their strong community outreach and engagement program—a critical component to addressing health inequities.”

As a clinician-investigator internationally recognized for her collaborative action-oriented

approaches in pursuit of equitable care, Dr. Battaglia is well aware of some of the challenges she faces in her new role. Inequitable healthcare, while recognized decades ago, became headline news early in the pandemic and remains so.

“The COVID pandemic and all the social injustices that were uncovered during that time period woke us up as a nation and demanded accountability on the part of healthcare systems, researchers, policymakers, and everyone,” Dr.

Battaglia said. “From my perspective it was like ‘It’s about time.’ People had been saying that inequities and disparities were important, but now there is an expectation and demand that you are actually going to do something about it.”

Recognizing the problem is a first step only, said Dr. Battaglia, who is Associate Cancer Center Director for Cancer Care Equity. “I do think, from my perspective, it’s still jargon. It’s words for many, without action.” Having a vision, committing resources, and doing the work collaboratively with the affected community is the more challenging next step, and that is what drew her to YCC.

“I’m most excited about [YCC Director] Eric Winer’s leadership…. He has this vision to create this unparalleled clinical oncology program in [Connecticut] and within that vision is [the goal of] ensuring that clinical excellence gets to everyone, equally,” Dr. Battaglia said. “That’s the shining star that will guide this new initiative.

“To be able to do it right you need to invest in it…bring in the right partners, and sometimes challenge the traditional approach of care delivery,” Dr. Battaglia said. “A lot of people who use inequity words and the phrases don’t understand, really, what it takes to actually do the work. It’s not pretty. It’s messy, and it takes intentionality, long-term commitment, and time.”

The pace of the work might not align perfectly with the pace of a traditional academic center, which is often driven by the sort of timelines, milestones, and benchmarks required by institutions such as the National Institutes of Health, Dr. Battaglia said.

“[Instead] sometimes we have to stop and slow down and listen and bring in people who are not traditional experts… bring them into the fold to help us design approaches, programs, and research that will actually improve the care of those who are most at risk,” she said.

Dr. Battaglia is speaking from experience, as

she explained in her December presentation at the Academy Health 16th Annual Conference on the Science of Dissemination and Implementation.

There she reported on an ambitious $9 million, fiveyear pragmatic clinical trial, a recently completed study on introducing oncology patient navigators into six Boston academic medical centers to help breast cancer patients from historically marginalized backgrounds get timely and quality cancer care.

The navigation intervention focused on identifying and removing social barriers to care, such as transportation, insurance, language, and childcare.

The study was supported by the infrastructure of the hospitals’ academic institutions—BU, Tufts, Harvard, and the University of Massachusetts— including strong regulatory data, informatics, community engagement, biostatistics, and more.

“But even with all that, the catalyst was the community that came together and demanded action. This study was unprecedented, in that it brought together competing institutions, to improve care for a hard-hit population of patients who were not being served equitably. And the hardest part of it was getting all the stakeholders to agree on an approach and to actually implement it.

“A lot of time and energy went into developing relationships, coalitions, advisory groups,” Dr. Battaglia said. “[And there was] making sure the clinicians had a voice, navigators had a voice, and patients had a voice, and then trying to integrate that to really change the way we were delivering care in the respective hospitals.”

The trial results were mixed. Successes included the establishment of a protocol across the six Boston hospitals, the implementation of tools to support navigation in the field, and sharing data across hospitals.

“Where we fell short was actually implementing the protocol and rolling it out in real life,” Dr. Battaglia said, noting that only about 50 percent of

“The COVID pandemic and all the social injustices that were uncovered during that time period woke us up as a nation and demanded accountability on the part of healthcare systems, researchers, policymakers, and everyone.”

Tracy Battaglia, MD, MPH

the patients eligible in the period got any navigation services at all. The study did show, however, that women who received the navigation protocol definitely did better, she said. “Their care was more timely and the quality of care was more complete.”

Some identified barriers included the lack of a consistent way to identify patients who needed navigation services, the burden of tracking and sharing data if it is not part of the existing electronic medical record, a hospital leadership commitment to providing resources, and prioritizing changes in traditional workflow.

Dr. Battaglia says there remains a great deal of data to consider, but one outcome is certain and persuasive — navigation improves care for those most at risk for cancer care inequity, and there is a dire need for public policy to make oncology patient navigators sustainable in the current care system. This work contributed to the Biden administration’s decision to include navigation in the CMS (Centers for Medicare & Medicaid Services) physician fee schedule for 2024.

“So, we’re making progress because we’re sharing data,” said Dr. Battaglia, who is founding chair of the National Navigation Roundtable and participated in several National Cancer Institute cooperative groups and, most recently, on the working group of the President’s Cancer Panel that is exploring technology that may advance navigation programs.

“The only reason we were successful at collaborating to begin with…was because the community

demanded it of us,” Dr. Battaglia said, adding that in addition to the COVID pandemic in the midst of the study, it also took on a personal element.

“In complete candor, I was diagnosed with breast cancer at the very outset of the study [and] that experience exemplified why we had to do this. When I was diagnosed with breast cancer, what happened? People rallied around me and got me right into excellent care.”

While thankful for their concern, Dr. Battaglia recognized the irony of getting the expert care she needed from a healthcare system she understands.

“That’s the problem right? I became more acutely aware of the inequities and more acutely aware of the need to pull in people with more diverse backgrounds. To do equity research you need to acknowledge your lived experience…my approach to this changed with that.”

March was a busy first month for Dr. Battaglia, who has already been busy building relationships, coalitions and partnerships as she learns how best to support patients, providers, and practices across the state.

At the same time, Dr. Battaglia said, “YCC is also discovering new treatments and new approaches, but if we are not intentional about making sure they are reaching everyone then the inequities will get worse. My job in the first year is to partner with key stakeholders and identify [situations] that are ripe for action-oriented interventions.” •

— Naedine Joy Hazell

First leader of the new Initiative to Address Cancer Inequities at YCC

GIFT GIVING FOR ALL SEASONS

Benefitting Science & Society

The excellence of the faculty and staffs at Smilow Cancer Hospital and Yale Cancer Center and the generosity of the donors and volunteers—that’s what has impressed and inspired Susan Roux, in her first few months as Assistant VP of Cancer Fundraising.

Helping potential donors explore opportunities for giving means first understanding their goal and aligning those with the priorities at Yale Cancer Center and Smilow Cancer Hospital. “Finding the place that they magically intersect—where need and intention really do meet. That’s where great

things can happen,” said Roux, noting the many opportunities afforded by the distinctive YCC/ Smilow partnership that supports pioneering clinical care informed by distinguished research by Yale scientists and physicians.

“[There’s] world-class expertise behind those

“Our donors are our partners….Our jobs as development professionals is to help our donors understand the impact that philanthropy can have.”

Susan Roux, Assistant VP of Cancer Fundraising

laboratory doors devoted to some of the biggest problems in cancer. Because it’s Yale and the work is so outstanding, it’s the type of philanthropy that can really accelerate [research] and really make a difference,” said Roux, who is new to Yale since September, but not new to philanthropy, having had leadership roles in development at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston.

“Our donors are our partners, so to not engage fully with them, then we’re just missing opportunities,” Roux said. “Our job as development professionals is to help our donors understand the impact that philanthropy can have.”

That impact can support many important initiatives that include community outreach to increase cancer awareness and screenings; a study of social determinants affecting diagnosis and treatment of the underserved or uninsured; a new support program for the burgeoning group of individuals diagnosed with cancer younger than age 50; or the breakthrough research that leads to novel therapies for patients.

“It is critical to spend the time to explain how philanthropy is so important to the whole continuum of research, education, patient care, and community outreach so that potential donors can envision the difference they want to make,” Roux said.

For example, donations that bolster a specific clinical program or a research program in its nascent stages are critical to help prove their value, making them eligible for future grant money.

“The NIH (National Institutes of Health) doesn’t fund good ideas,” Roux said. “It funds good ideas that have been shown to have a solid pathway

that could lead to an important discovery” or, for example, make progress in addressing inequitable care.

Tightening research dollars means there is more competition for less. A June 2023 study published in The Lancet Oncology found that of the $24.5 billion in global cancer research money, allocated in the five-year period 2016-2020, funding “decreased year-on-year, with the largest drop observed between 2019 and 2020.”

With less than a year into her new job, Roux already has some overall goals, including increased stewardship, easier access for potential donors, and an expanded Director’s Council of outside advisors. New members would be people “who really want to roll up their sleeves and get educated about the work that’s happening here,” including the impactful clinical programs and the scientific advances in treating and preventing cancer.

Increased stewardship will include more communication with donors, so that they are aware of progress being made in novel research thanks to their philanthropy.

“You can’t tell half a story. We need to share the impact that donors are having. We don’t want to stop at the gift being made,” Roux said. Taking someone along on the journey is very powerful and inspiring

“People should know what a gem we have right here.” •

— Naedine Joy Hazell

CANCER CENTER MEMBERS BY RESEARCH PROGRAM

CANCER IMMUNOLOGY

Marcus Bosenberg*

David Braun

Grace Chen

Lieping Chen

Joseph Craft

Peter Cresswell

William Damsky

Vishwa Deep Dixit

Richard Edelson

Brinda Emu

Richard Flavell

Francine Foss

Jorge Galan

Michael Girardi

Ann Haberman

David Hafler

Stavroula Hatzios

Kevan Herold

Andres Hidalgo

Ya-Chi Ho

Jeffrey Ishizuka

Akiko Iwasaki

Nikhil Joshi

Paula Kavathas

Steven Kleinstein

Smita Krishnaswamy

Priti Kumar

Mark Lee

Carrie Lucas

Stacy Malaker

CANCER PREVENTION AND CONTROL

Prasanna Anant

Bubu Banini

Elizabeth Berger

Krysten Bold

Elizabeth Claus

Nicole Deziel

Michaela Dinan*

Lisa Fucito

Jacquelyne Gaddy

Veda Giri

Mehra Golshan

Rachel Greenup

Cary P. Gross

Scott Huntington

Melinda Irwin

Caroline Johnson

Benjamin Judson

Amy Justice

Grace Kong

Suchitra Krishnan-Sarin

Michael Leapman

Maryam Lustberg

CANCER SIGNALING NETWORKS

Anton Bennett

Titus Boggon

David Calderwood

Gary Desir

Michael DiGiovanna

Rong Fan

Kathryn Ferguson

Carlos FernandezHernando

Clare Flannery

Sourav Ghosh

Valentina Greco

Mark Hochstrasser

Robert Homer

* denotes program leaders

Valerie Horsley

Won Jae Huh

Peter Humphrey

Michael Hurwitz

Richard Kibbey

Isaac Kim*

Jiyeon Kim

Joseph Kim

Daryl Klein

Anthony Koleske

Mark Lemmon

Andre Levchenko

Yansheng Liu

Michael Mak

Mark Mamula

Ruslan Medzhitov

Kathryn Miller-Jensen

Ruth Montgomery

Walther Mothes

Markus Müschen

Kelly Olino

Noah Palm

Tristen Park

Joao Pereira

Jordan Pober

Anna Marie Pyle

Aaron Ring

Carla Rothlin*

Kurt Schalper

David Schatz

Stuart Seropian

Brian Smith

Edward Snyder

Xiaolei Su

Mario Sznol*

Thuy Tran

John Tsang

Kiran Turaga

Juan Vasquez

Gavitt Woodard

Yong Xiong

Shuangge Steven Ma

Xiaomei Ma*

Sherry McKee

Linda M. Niccolai

Marcella Nunez-Smith

Stephanie O’Malley

Hermine Poghosyan

Ilana Richman

Rozalyn Rodwin

Joseph Ross

Tara Sanft

Sarah Schellhorn

Andrea Silber

Mehmet Sofuoglu

Donna Spiegelman

Sakinah Suttiratana

Tamar Taddei

Emily Wang

Shi-yi Wang

Xiao Xu

Darryl Martin

Peggy Myung

Michael Nathanson

Don Nguyen*

Rachel Perry

Daniel Petrylak

Katerina Politi*

David Rimm

Jesse Rinehart

Matthew Rodeheffer

Joseph Schlessinger

Martin Schwartz

Gerald Shulman

David Stern

Edward Stites

Yajaira Suarez

Kaelyn Sumigray

Derek Toomre

Benjamin Turk

Robert Weiss

Dianqing Wu

John Wysolmerski

Yang Yang-Hartwich

Xiaoyong Yang

CANCER CENTER MEMBERS BY RESEARCH PROGRAM

DEVELOPMENTAL THERAPEUTICS

Karen Anderson*

Masoud Azodi

Joachim Baehring

Aarti Bhatia

Nicholas Blondin

Barbara Burtness*

Michael Cecchini

Herta Chao

Yung-Chi Cheng

Anne Chiang

Zachary Corbin

Jason Crawford

Craig Crews

Henk De Feyter

Hari Deshpande

Barbara Ehrlich

Jonathan Ellman

Donald Engelman

Tarek Fahmy

James Farrell

Scott Gettinger

Sarah Goldberg

Andrew Goodman

Lohith Gowda

Ya Ha

Roy Herbst

Seth Herzon

Iris Isufi

William Jorgensen

Patrick Kenney

Harriet Kluger

Jeremy Kortmansky

Ian Krop

Pamela Kunz

Jill Lacy

Brett Lindenbach

Elias Lolis

Patricia LoRusso

David Madoff

Jennifer Moliterno Gunel

Viswanathan Muthusamy

Natalia Neparidze

Antonio Omuro

Terri Parker

Farzana Pashankar

GENOMICS, GENETICS, AND EPIGENETICS

Nita Ahuja

Claudio Alarcon

Arnaud Augert

Mathieu Bakhoum

Susan Baserga

Kim Blenman

Demetrios Braddock

Sidi Chen

Keith Choate

Andrew Dewan

Nadya Dimitrova

Salil Garg

Mark Gerstein

Antonio Giraldez

Murat Gunel

Shangqin Guo

Ruth Halaban

Stephanie Halene

Gloria Huang

Anita Huttner

Farren Isaacs

Yannick Jacob

Dhanpat Jain

Lucia Jilaveanu

Samuel Katz

Sajid Khan

Yuval Kluger

Diane Krause

John Kunstman

David Leffell

Peining Li

Haifan Lin

RADIOBIOLOGY AND RADIOTHERAPY

Ariyan Aneja

Ranjit Bindra

Justin Blasberg

Franziska Bleichert

Daniel Boffa

Douglas Brash

Zhengxin Cai

David Carlson

Richard Carson

* denotes program leaders

Sandy Chang

Zhe Chen

Veronica Chiang

Joseph Contessa*

Shari Damast

Jun Deng

Frank Detterbeck

Daniel DiMaio

James Duncan

Chen Liu

Xavier Llor

Jun Lu

Charles Lusk

Shrikant Mane

I. George Miller

Mandar Muzumdar

Sigrid Nachtergaele

Karla Neugebauer

James Noonan

Curtis Pickering

Manoj Pillai

Lajos Pusztai*

Mariya Rozenblit

Peter Schwartz

Jason Sheltzer

Nikolai Podoltsev

Michal Rose

William Mark Saltzman

Alessandro Santin

Rory Shallis

David Spiegel

Preston Sprenkle

Stacey Stein

Mario Strazzabosco

Richard Sutton

Vasilis Vasiliou

Eric Winer

Amer Zeidan

Jiangbing Zhou

Luisa Escobar-Hoyos

Suzanne Evans

Peter Glazer

James Hansen

Thomas Hayman

D.S. Fahmeed Hyder

Ryan Jensen

Lilian Kabeche

Megan King*

Zachary Smith

Joan Steitz

Hugh Taylor

Jeffrey Townsend*

Zenta Walther

Zuoheng Wang

Sherman Weissman

Craig Wilen

Frederick Wilson

Andrew Xiao

Mina Xu

Qin Yan*

Hongyu Zhao

Breakthroughs is published annually to highlight research and clinical advances from YCC and the Smilow Cancer Hospital

ART & PRODUCTION

EDITOR

Naedine J. Hazell

CONTRIBUTORS

Renee Gaudette

Meena Moran

Evan Morris

Rosa Munoz Xicola

Henry Park

Abhijit Patel

Timothy Robinson

Faye Rogers

Christopher Tien

Yale Cancer Center

2 Church Street South, Suite 112 New Haven, CT 06519 naedine.hazell@yale.edu

Emily Montemerlo

Rebecca Shannonhouse

Nicole Wise

Yang Zhou

PRODUCTION

Designer: Chris Moore

Illustrator: Danielle Ferretti

Proofreading: LuAnn Bishop

Printing: Yale Printing & Publishing Services

CANCER CENTER 333 Cedar Street PO Box 208028

New Haven, CT 06520-8028 yalecancercenter.org