For decades, a weakened immune system has been considered an unavoidable side effect of receiving radiation or chemotherapy. These treatments, while highly effective at killing cancer cells, also deplete the body’s store of blood stem cells and damage the area in the bone marrow where new ones are produced. Blood stem cells, also known as hematopoietic stem cells (HSCs), are critical for a functioning immune system because they give rise to all other blood cells, including white blood cells.

An effective immune system response requires coordination among many types of immune cells, including CD4+ (helper) T cells, CD8+ (cytotoxic) T cells, and B cells. Helper T cells recognize antigens—identifying molecules on the surface of a pathogen—and release warning signals. These signals activate cytotoxic T cells, which kill the infected or cancerous cells, and B cells, which produce antibodies to attack the pathogen directly.

Immune checkpoint inhibitors (ICI), which help immune T cells identify and kill tumor cells, are most effective in patients who have tumor antigen-specific T cells in circulation. Studies have shown that patients with ovarian cancer do have such tumor-reactive T cells in their blood, indicating a “naturally occurring, antitumor immune response.” So why do only 10-15% of ovarian cancer patients respond favorably to ICI therapy? This was the question former Damon Runyon Clinical Investigator Ronald J. Buckanovich, MD, PhD, and his team at the University of Pittsburgh set out to answer in a recent study.

The Damon Runyon Cancer Research Foundation has announced its newest cohort of Damon Runyon Fellows, 13 outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators. This prestigious, four-year Fellowship encourages the nation's most promising young scientists to pursue careers in cancer research by providing them with independent funding ($231,000 total) to work on innovative projects.

A growing body of evidence links the gut microbiome—the vast collection of bacteria and other microorganisms that live in the digestive tract—to the body’s immune response to cancer. But the role of specific bacteria, and the nature of their interaction with immune cells, remain a critical subject of research. A better understanding of the crosstalk between the gut microbiota and the immune system would allow us, among other strategies, to use probiotics as part of cancer treatment.

‘‘All happy families are alike; each unhappy family is unhappy in its own way.’’ This principle, borrowed from Leo Tolstoy, is how Damon Runyon alumni Pavan Bachireddy, MD, and Catherine J. Wu, MD, summarized the conditions of immunotherapy response and resistance in a recent study.

The Damon Runyon Cancer Research Foundation has announced ten recipients of the 2022 Damon Runyon-Rachleff Innovation Award, established to support “high-risk, high-reward” ideas with the potential to significantly impact the prevention, diagnosis, or treatment of cancer. Five initial grants of $400,000 over two years have been awarded to six extraordinary early-career researchers (four individuals and one collaborative team), each of whom will have the opportunity to receive two additional years of funding (for a total of $800,000). This year, “Stage 2” continuation support was granted to four Innovators who demonstrated significant progress on their proposed research during the first two years of the award.

Current imaging technology allows scientists to view tissue samples at such high resolution that they can gather information about individual cells. Looking at a high-resolution image of a tumor, for example, an oncologist can locate and measure the amount of a specific mutant protein in a cancer cell. The information gleaned from image-based single-cell analysis can aid both in diagnostics and tracking disease progression.

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.