Grant: Travel Awards - Institute Community Support

Colorectal cancer is the second most common cause of cancer deaths. Treatment for individuals with this cancer include surgery followed by chemotherapy. Chemotherapy is not always effective, and nearly half of the patients will develop a recurrence of their disease. Recently, a new cancer strategy has been developed, called immunotherapy. It uses the body's own immune system to fight cancer. It has shown promise in relapsed disease. Unfortunately, only about 15% of colorectal cancer patients benefit from it. Recent discoveries suggest that certain proteins, called immune checkpoints, expressed by cancer cells might help regulate cancer growth and failure to respond to therapy. The immune checkpoints are like gatekeepers that control the immune system's response to cancer. If we understand how these immune checkpoints function, then we can improve upon therapies that are being developed to treat cancers. In our early research, we looked at colorectal cancer cells that became resistant to chemotherapy. We discovered that these resistant cells had more of one of the checkpoint proteins, called PD-1, when compared to chemo-sensitive cells. With these interesting discoveries, we have started to learn more about why colorectal cancer cells are making PD-1 and how it affects colorectal cancer development. Our data told us two important things: (1) Colorectal cancer cells and tumor samples of colorectal cancer from patients have PD-1. The more PD-1 they have, the more aggressive the tumor seems to be. (2) When we manipulated and reduced PD-1 in colorectal cancer cells in culture, using genetic methods or FDA-approved drugs, the cancer cells grew more slowly, and they responded better to drugs. We therefore believe that having high levels of PD-1 in colorectal cancer cells prevents the cells from responding to chemotherapy drugs. By solving these mysteries, we hope to find better ways to treat colorectal cancer and bring hope to people battling this devastating disease.