Like living species, cancer cell populations undergo evolution. They accumulate mutations and become heterogeneous, and the mutations that increase chances of survival become more common. In this way, a single genetic alteration can evolve into a tumor and eventually spread throughout the body. Understanding the evolutionary path that tumors follow, from a single-cell mutation to metastatic cancer, is essential for designing effective clinical interventions. However, environmental factors and other variables can confound efforts to trace a cancer’s development from beginning to end.

Cancer treatment decision-making depends on an accurate understanding of a patient’s prognosis. Mistaking a cancer’s aggressiveness can lead to either under- or overtreatment, both of which carry increased risk of fatality. Current methods of prognostication, which usually rely on examining cancerous tissue via X-ray or microscope, involve subjective judgments and sometimes fail to predict disease course. With the rise of DNA sequencing technologies, clinicians are increasingly looking to patients’ genomes for clues about how their cancer will behave.

The Damon Runyon Cancer Research Foundation has named five new Damon Runyon Clinical Investigators. The recipients of this prestigious award are outstanding, early-career physician-scientists conducting patient-oriented cancer research at major research centers under the mentorship of the nation's leading scientists and clinicians.

Last fall, we published the story of Damon Runyon Clinical Investigator Jennifer M. Kalish, MD, PhD, a pediatric geneticist at the Children’s Hospital of Philadelphia who has dedicated her career to the study of Beckwith-Wiedemann Syndrome (BWS), a rare genetic condition that causes overgrowth in certain parts of the body and predisposes children to cancers of the kidney and liver. As Founding Director of the hospital’s Beckwith-Wiedemann Syndrome Clinic, Dr. Kalish established the country’s first and only active BWS patient registry and biorepository storing blood and tissue samples necessary for research. In December 2020, her lab unveiled the first human cell-based model of the syndrome, developed using cells from patients in the registry.

The Damon Runyon Cancer Research Foundation celebrated 75 years of funding cancer research at Gotham Hall in New York on June 1, 2022. The event raised nearly $1 million to support promising early-career scientists pursuing innovative strategies to prevent, diagnose, and treat all forms of cancer.

Immune checkpoint inhibitors work by releasing the “brakes” on immune T cells, unleashing them upon cancer cells. After the discovery of two of these brakes, PD-1 and CTLA-4, and the subsequent cascade of drugs targeting them, the search for new checkpoints to target stalled. But this spring, the FDA approved a new melanoma drug called relatlimab, which targets LAG-3—the first new checkpoint in almost a decade.

Damon Runyon alumni Ash Alizadeh, MD, PhD, and David Kurtz, MD, PhD, and others have shown that cancer can be detected via blood sample by measuring circulating tumor DNA (ctDNA). This approach, however, requires high concentrations of tumor DNA in the bloodstream and provides low resolution—in other words, it can detect cancer but cannot identify a specific cancer subtype.

Just before dawn on Monday, October 4, 2021, David Julius, PhD, a longtime Damon Runyon mentor and former Fellowship Award Committee member, and Ardem Patapoutian, PhD, a former Damon Runyon awardee, received news that they had won the Nobel Prize for Physiology or Medicine. The award recognized the two scientists’ independent “discoveries of receptors for temperature and touch.” Ardem and his team at Scripps Research discovered the Piezo channel proteins, essential for our sense of touch. For David, the Nobel culminated over three decades of research at the University of California, San Francisco, on the proteins that help us sense temperature and pain.

Cells absorb hormones, proteins, and other molecules from their environment through a process called endocytosis. In this process, the molecule being absorbed—the “cargo”—binds to a receptor on the surface of the cell membrane, recruiting a protein called clathrin to the inside of the cell membrane. The membrane then pinches inward to form a clathrin-coated vesicle with the cargo protected inside. Endocytosis is mediated by a protein complex called AP2, which links the cargo-bound receptors to the clathrin coat (see below). The functionality of AP2 depends on its shape. When “closed,” it can only bind to the cell membrane; when “open,” it can bind to cargo-bound receptors and clathrin proteins. But how exactly it makes this conformational change from “closed” to “open” has long been unclear. 

Three scientists with exceptional promise and novel approaches to fighting cancer have been named the 2022 recipients of the Damon Runyon Physician-Scientist Training Award. The awardees were selected through a highly competitive and rigorous process by a scientific committee comprised of leading cancer researchers who are themselves physician-scientists.