Uncovering the Dark Matter of Cancer, ft. Dr. Bernie Fox

Dr. Patrick Hwu sits down with Dr. Bernie Fox, a pioneering immunologist and chief of the Laboratory of Molecular and Tumor Immunology at Providence Cancer Institute. The conversation spans the early days of immunotherapy, including their shared training roots in the NIH Surgery Branch under Dr. Steve Rosenberg, and moves into today’s cutting-edge science. Dr. Fox explains the emerging concept of “dark matter” in cancer biology — the once-dismissed non-coding regions of DNA that may play a pivotal role in tumor progression and immune targeting. He discusses how these regions are now known to produce short-lived proteins that may act as cancer drivers and immunotherapy targets. Importantly, many of these “dark antigens” are shared across tumor types and do not appear in healthy tissue, making them promising targets for vaccines, TCR therapies, and other immune-based treatments. The episode also highlights Fox’s commitment to mentorship, the evolution of the Society for Immunotherapy of Cancer (SITC), and the future potential of dark genome research in cancer and beyond. What You'll Learn • How early immunotherapy research at the NCI helped prove that genetically engineered T cells can fight cancer. • What scientists mean by the “dark genome” and why it matters in cancer. • How hidden regions of DNA can produce proteins that help tumors grow and spread. • Why many tumor antigens may come from non-canonical DNA regions rather than mutations. • How researchers are exploring vaccines and engineered T cells to target these antigens. • Why discoveries in the dark genome could impact many diseases beyond cancer.