Sean Pitroda, MD

Recently, immunotherapies, which reactivate one’s own immune system to fight off cancer, have revolutionized lung cancer treatment. Unfortunately, less than half of patients respond to immunotherapy. One reason is due to cancer’s ability to disguise itself and hide from the immune system. Recently, we discovered a completely new way that lung cancers use to hide from the immune system. We will utilize cutting-edge genetic technologies to uncloak immune-evasive lung cancers in an effort to improve the response to potentially life-saving immunotherapy treatment. We will focus on the process of splicing, which occurs before protein synthesis. It involves cutting out and rearranging sections of messenger RNA (mRNA), which is necessary for protein production. We will target the underlying mechanism(s) responsible for splicing dysfunction involved in lung cancer. By understanding how lung cancers evade one’s own immune system, we may be able to improve the long-term survival of patients with metastatic non-small cell lung cancer.

Update:
We have made strong progress this year. We identified a previously unknown cancer-causing mechanism driving the “splicing factor” SRSF10 gene in lung cancer. In addition, we characterized novel immune-suppressive effects of SRSF10 in lung cancer. We anticipate that data generated through this proposal will ultimately inform novel strategies to combine RNA splicing modulators with immunotherapy to improve outcomes for patients with metastatic non-small cell lung cancer, thereby advancing the paradigms for cancer treatment.