Until the early 2000s, cancer was largely treated with a one-size-fits-all approach. With the rise of targeted therapies over the last two decades, clinicians can now match many patients with the treatment most likely to be effective for them, based on the specific cancer-causing mutation(s) in their genes.

Instrumental to this rise was Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ’95–’98), who in 2006 led a team of scientists in an ambitious project: to assemble genomic data from more than 11,000 tumors across 33 different cancer types. Since its completion in 2018, the Cancer Genome Atlas (TCGA) has proven invaluable to scientists working to develop new treatments and understand how patients respond to existing treatments.

In his own lab at the Dana-Farber Cancer Institute, Matthew now mentors young scientists applying genomic analysis to pressing research questions in the era of targeted therapy. Among these mentees is former Damon Runyon Fellow Tikvah K. Hayes, PhD, who studies the genomes of small cell lung cancer tumors to uncover mechanisms of treatment resistance. By investigating how tumors evolve in response to drugs, and what genetic markers may predict drug resistance, Tikvah aims to improve patient treatment protocols. Her work incorporates not only data from TCGA, but also insights from its creators. “I call the Damon Runyon network my science fraternity,” she says with a laugh. “Because we have this rich history dating back to the 1940s. It’s an awesome thing to be part of.”

Gordon J. Freeman, PhD (Damon Runyon Fellow ’79–’81), was critical in the discovery of the programmed cell death-1 (PD-1) receptor pathway, which keeps immune T cells from attacking the body’s own cells. This discovery made immunotherapy possible, as scientists realized that removing the PD-1 mediated “brake” on immune activity would unleash the body’s defense mechanisms against cancerous cells. Gordon’s work led directly to the development of pembrolizumab (Keytruda), one of the earliest immunotherapies approved by the FDA, which is now used to treat melanoma, certain lung cancers, triple-negative breast cancer, and other metastatic or advanced-stage cancers.

But the work does not end with FDA approval. Some patients treated with immunotherapies experience immune-related adverse events (irAEs), which can be as minor as a fever and as serious as deadly heart inflammation. This “Achilles’ heel of immunotherapy” is where current Damon Runyon-Rachleff Innovator Alexandra-Chloé Villani, PhD, is focusing her research efforts. “While the advent of immunotherapies is revolutionizing cancer treatment and providing new hope for patients,” Chloé says, “I have witnessed firsthand the toll this cancer treatment can take on the body.” In her Massachusetts General Hospital lab, she analyzes patient samples using state-of-the-art genomic technologies to understand why and how these irAEs occur. Beyond improving patient care through better management of these side effects, her research may also improve the lifesaving potential of immunotherapy drugs (like pembrolizumab) by enabling patients to undergo longer treatment regimens.

Physician-scientists, uniquely positioned at the interface between the clinic and the lab, are essential to the translation of scientific discovery into effective therapies. Many medical school graduates are deterred from pursuing the physician-scientist career path because of the training and costs required. Damon Runyon is one of very few organizations to address these barriers directly. Our Clinical Investigator Award and Physician-Scientist Training Award build the ranks of physician-scientists by offering dedicated financial support, including medical school debt relief, and mentorship to scientists embarking on this path.

The earliest recipients of these awards are now among the most influential figures in cancer research. Renier J. Brentjens, MD, PhD (Damon Runyon Clinical Investigator ‘06–’11), through his work in the lab and in clinical trials, established CAR T-cell immunotherapy as a treatment for leukemia. Jedd D. Wolchok, MD, PhD (Damon Runyon Clinical Investigator ‘03-’08), led the clinical trials of Yervoy, one of the first immunotherapies approved by the FDA in 2011. These are just a few examples of groundbreaking discoveries by Damon Runyon physician-scientists that have changed patient care.

Their success in bringing insight from the clinic to the laboratory, and vice versa, paved the way for a new generation of physician-scientists. As a current Clinical Investigator, Heather L. Yeo, MD, is developing an app to help manage care for patients undergoing surgery for gastrointestinal cancer, with the goal of preventing post-operative complications and readmissions. Karuna Ganesh, MD, PhD, another Clinical Investigator, is growing three-dimensional models of colorectal cancer from patient samples to study how cancer spreads from its tissue of origin and identify opportunities to stop the metastatic process.

“There is no greater privilege than being entrusted with a fellow human’s life,” Karuna wrote in Nature earlier this year. “The ability to combine such responsibility with curiosity-driven scientific inquiry and the potential to positively influence many lives brings tremendous meaning and joy to the day’s work.”

A pioneer in stem cell research, Elaine V. Fuchs, PhD (Damon Runyon Fellow ’77–’79), is credited for uncovering the mechanisms by which tissue stem cells regenerate dying cells and heal tissue wounds. Her research also revealed the role that stem cells play in tumor growth and treatment resistance: as these long-lived cell lines accumulate mutations, they begin producing an arsenal of molecular weapons that enables them to survive chemotherapy and immunotherapy.

In 2009, while Elaine was being presented the National Medal of Science by President Barack Obama, current Damon Runyon Fellow Alain R. Bonny, PhD, was starting his research career in a biochemistry lab at Penn State. At the time, his mother was undergoing treatment for breast cancer. “I began to appreciate the indelible link between fundamental and translational research,” he says. “Specifically, how we can leverage a thorough understanding of how normal tissue behaves in order to study and ultimately treat pathological conditions, namely cancer.” Now, as a postdoctoral fellow in Elaine’s lab, Alain is leveraging his mentor’s foundational research to do just that. He studies the body’s response to acute skin injury, as these signal pathways bear a striking resemblance to squamous cell carcinoma development. Understanding how healthy tissue moves from inflammation to healing may shed light on how squamous cell carcinoma and other cancers exploit these signaling mechanisms.

“I love to see the postdocs in my lab pursue the questions they’re passionate about,” Elaine says. “That’s when they start thinking outside the box—when they become fearless. If you teach your students to do this, everything else will fall into place.”