Sidi Chen, Ph.D., CLIP Investigator Yale University

Metastatic melanoma has historically been one of the hardest cancer types to treat successfully. While checkpoint immunotherapy—which can unleash the immune system against tumors—has improved care for a significant fraction of this patient population, most patients still don’t benefit, and the genetic factors that directly influence whether or not patients will respond to treatment are largely unknown. Therefore, using an established animal model of melanoma, Dr. Chen is performing high-throughput genetic screens in order to discover which cancer cell factors control the effectiveness of checkpoint immunotherapy.

Initially, Chen’s team is aiming, in a mouse model of melanoma, to systematically identify pathways that could be targeted to improve checkpoint immunotherapies targeting the PD-1/PD-L1 pathway. Then, they will see if any of these “hits” are also found in melanoma patients’ clinical signatures as well as how they’re related to immunotherapy responses. Lastly, they will target the relevant pathways in mice in combination with immunotherapy to see if the combination improves outcomes. If successful, these experiments will establish novel genes that can serve as biomarkers for better prediction of response to and new targets for combination strategies that could apply to cancer types beyond melanoma.

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