In the latest episode of The Genetics Podcast, Patrick Short was joined by Dr. Luis Diaz, head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center. Known for his contributions to precision oncology, Dr. Diaz has played an important role in the development of targeted therapies and immunotherapies that are reshaping cancer care. The discussion spans his landmark studies, the evolution of liquid biopsies, and the potential for precision medicine to expand into other fields. Here's a quick recap of the conversation:
Dr. Diaz began by sharing the story of his recent trial that achieved a 100% complete response rate in patients with mismatch repair-deficient rectal cancer—a rare and extraordinary achievement in oncology. These patients, who would typically undergo chemotherapy, radiation, and life-altering surgery, were instead treated with six months of immune checkpoint inhibitors.
The results were remarkable: tumors disappeared entirely in all patients, eliminating the need for invasive follow-up treatments. This success is now being applied to other mismatch repair-deficient cancers, such as those in the stomach, pancreas, and bladder. “Our focus is on cancers where surgery can be devastating,” Dr. Diaz explained, “to improve outcomes and help patients maintain a better quality of life.”
This breakthrough stems from decades of research into Lynch syndrome, a hereditary condition tied to mismatch repair deficiency in colorectal cancer. Dr. Luis Diaz explained how this genetic signature results in tumors with extremely high mutation rates, making them highly visible to the immune system.
By using immune checkpoint inhibitors, his team used the immune system’s natural ability to identify and destroy these tumors. This approach has transformed the way mismatch repair-deficient cancers are treated and led to the first FDA tumor-agnostic approval, allowing the therapy to be used across various cancer types sharing this genetic marker.
Dr. Diaz also discussed his pioneering work on liquid biopsies, a non-invasive method for detecting cancer by analyzing tumor-derived DNA in the blood. This technique offers a real-time snapshot of cancer progression, treatment response, and even resistance to therapy.
“We’ve shown that after surgery, the presence of circulating tumor DNA can predict recurrence with incredible accuracy,” said Dr. Diaz. This innovation has sparked the growth of companies like GRAIL and Guardant Health, which are working to bring early cancer detection tests to market. While challenges remain, particularly in detecting very early-stage cancers, Dr. Diaz is optimistic about the potential for liquid biopsies to revolutionize cancer care.
Looking to the future, Dr. Diaz touched on emerging opportunities in cancer prevention and the application of precision medicine to other fields, such as autoimmune and cardiovascular diseases. In a recent study, his team explored the use of immune checkpoint inhibitors to delay or prevent cancer in patients with Lynch syndrome, showing promising results. “This opens up the possibility for immunoprevention,” he said, “a concept that could fundamentally change how we approach cancer risk in high-risk populations.”
Dr. Diaz also highlighted ongoing research into using liquid biopsy technologies for early detection and monitoring of non-cancer diseases, such as autoimmune disorders and brain conditions.
Dr. Diaz’s work showcases the power of collaboration between cutting-edge science and patient-centered care. His breakthroughs in immunotherapy and liquid biopsies demonstrate how genetics can guide more effective, less invasive treatments—not just for cancer, but potentially for other complex diseases.