Irving Cancer Drug Discovery Program

Peter D. Canoll, MD, PhD, Jeffrey N. Bruce, MD and Brent Stockwell, PhD are testing the ability of a newly developed drug delivery device to deliver a novel compound that can kill tumor cells by a mechanism of cell death called ferroptosis. The team will perform safety studies in preparation for a future clinical trial. 

Cell-based immunotherapy is a personalized treatment that kills cancer by using the patient’s own immune cells. The development has been revolutionary for certain blood cancers, but progress has stalled in solid tumors, which make up 90% of all cancer diagnoses. Jordan S. Orange, MD, PhD, believes this is because the immune cells are specialized for a one-at-a-time killing approach that is easily overwhelmed and suppressed in solid tumors. He plans to find an irreversible small molecule that can turn a patient’s immune cells into “grenades” that engage in multi-directional killing of solid tumor cells.

Prostate cancer represents the second leading cause of cancer death in American men. Some aggressive forms of prostate cancer, such as neuroendocrine prostate cancer, still lack effective treatments. Michael M. Shen, PhD aims to develop an innovative category of small molecules that target NSD2, an enzyme that is up-regulated in neuroendocrine prostate cancer.

From the lab of Ben Izar, MD, PhD  comes a groundbreaking approach to treating non-small cell lung cancer (NSCLC) deficient in STK11 by targeting chromosomal instability (CIN) via the inhibition of the cGAS signaling pathway. This innovative strategy aims to develop a small molecule immunotherapy capable of restoring immune response against these aggressive tumors. Given the poor prognosis and resistance to current immunotherapies observed in STK11-deficient NSCLC, Izar's research addresses a critical unmet need in the field. Through a meticulously designed research plan, including in vivo efficacy studies and the development of novel cGAS inhibitors, the project aims to pave the way for a transformative treatment paradigm for STK11-deficient NSCLC and potentially other CIN-high cancers.

Every year, 400,000 cancer patients in the US receive treatment with anti-PD-1 antibodies, a type of immunotherapy that releases a brake on the anticancer actions of T cells. However, only about 25% of patients respond well. Seeking to improve outcomes, the Adam Mor, MD, PhD, discovered a new protein called PAG that acts as a checkpoint on T cells, limiting their cancer-killing actions.