When Megan Miller was twenty weeks pregnant, the doctors at Children’s Hospital of Philadelphia (CHOP) noticed her baby was unusually large for his gestation age. After further examination, Megan was informed that he likely had a condition known as Beckwith-Wiedemann Syndrome—a diagnosis she had never heard of. Naturally, the expecting mother consulted Google, where she found alarmingly little information. “The only place that had good scientific facts,” she recalls, “was CHOP’s website.”

Typically, when scientists discover a cancer-causing mutation, the goal is to develop a molecule that blocks the protein produced by the mutated gene. But for cancers driven by mutations in the KRAS gene—which include non-small cell lung, colorectal, and pancreatic cancers—this path to drug development has long been thwarted. The mutated KRAS gene encodes for a protein that releases continuous “grow” signals, causing cells to proliferate uncontrollably. For 40 years, this mutant protein was considered “undruggable,” its surface too smooth for a therapeutic molecule to bind. Then, after screening nearly 500 different molecules, a team at the University of California, San Francisco (led by Kevan M. Shokat, PhD, mentor to several Damon Runyon Fellows and former Damon Runyon-Rachleff Innovation Award Committee Member) discovered one that locks into a hidden crevice in the protein, stopping its activity. Even better, this hidden crevice only exists in the mutant version of the protein, meaning the molecule only targets cancerous cells—sparing healthy cells.

Each year, the Damon Runyon-Jake Wetchler Award for Pediatric Innovation is given to a third-year Damon Runyon Fellow whose research has the greatest potential to impact the prevention, diagnosis, or treatment of pediatric cancer. This year, the award recognizes the work of Peng Wu, PhD, a Damon Runyon-Sohn Pediatric Cancer Fellow at Stanford University.

Matthew G. Vander Heiden, MD, PhD, former Damon Runyon Innovator and current mentor, says he gets a lot of questions from his cancer patients about how their diet might impact disease progression. Often, these patients have heard the hypothesis that an aggressively calorie-restricted diet or the low-carbohydrate, high-fat ketogenic diet may slow tumor growth. The logic for these diets is that cancer cells require high levels of glucose to fuel their rapid proliferation, so depriving them of sugar might throw a wrench in the works. However, as Damon Runyon Fellow Evan C. Lien, PhD, a postdoc in Dr. Vander Heiden’s lab at MIT, put it: “A lot of the advice out there isn’t necessarily based on very good science.”

Like a leaky gas pipe in an apartment building, failure to repair DNA damage can have disastrous consequences, including the introduction of cancer-causing mutations. This is why our cells have complex mechanisms for recognizing and repairing broken DNA strands before too much damage has been done. In a big-picture sense, we know how DNA repair works: proteins responsible for sensing damage activate a cascade of other proteins, depending on the nature and location of the problem. But a granular understanding of this process, including which genes are involved, continues to elude scientists.

Prostate cancer is among the most common cancers in American men, accounting for one in five new cancer diagnoses. Hormone therapy is currently the standard of care for patients with metastatic disease, but nearly all patients develop resistance to this treatment eventually. Extensive effort has therefore been directed toward the search for new drug targets, illuminating the biological underpinnings of the disease. Given a tumor sample from a patient with prostate cancer, researchers can now identify millions of genetic and molecular features, from single DNA mutations to RNA transcription errors to mutant protein complexes.

Epidermal growth factor receptor (EGFR) is a protein on the surface of cells that receives signals telling the cell to grow. Mutations in the EGFR gene are known to drive a number of cancers, including non-small cell lung cancer. For patients with common EGFR mutations, known as “classical mutations,” EGFR inhibitor treatments are available and effective. But such targeted therapies have not been developed for patients with atypical mutations, often leaving chemotherapy as the only treatment option.

The National Academy of Medicine provides independent, evidence-based scientific advice to address national and global health challenges. Membership is considered to be one of the highest honors in the medical field and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. This year, four Damon Runyon alumni were nominated for membership, bringing the total number of Damon Runyon scientists in the organization to 41.

We are delighted to announce that Damon Runyon-HHMI Fellow Tyler Starr, PhD, of Fred Hutchinson Cancer Research Center, has been named a 2021 STAT Wunderkind. This award, granted annually to “the best early-career researchers in health and medicine in North America,” recognizes Tyler’s exceptional promise in the study of viruses and our immune systems.

Breast cancer is the most common cancer diagnosed in women worldwide, and an estrogen receptor known as ERα plays a critical role in more than 70% of these cancers. In healthy cells, when bound to estrogen, ERα activates a signaling pathway that controls cell growth, proliferation, and survival. In breast cancer, an abnormal variant of ERα sends this pathway into overdrive. For patients with ERα-positive breast cancer, estrogen-blocking hormone therapies like tamoxifen can prolong survival. Up to half of these patients will acquire resistance, however, creating an urgent need for novel treatment strategies targeting ERα.