Previously Funded Research

Israel Cañadas Castillo, PhD

Fox Chase Cancer Center

Research Project:

Co-opting endogenous retroviral signaling as a lung cancer vulnerability

Summary:

Both small-cell and non-small cell lung cancers contain different subpopulations of cancer cells, a feature known as tumor heterogeneity. While this cell heterogeneity is a key determinant of cancer progression and drug resistance, how it impacts the immune system in lung cancer patients remains incompletely defined. Dr. Cañadas recently identified a group of genetic elements known as Endogenous Retroviruses (ERVs) that are altered in certain drug-resistant populations of lung cancer cells. He showed that signaling from these ERVs promotes tumorigenesis, but that these retroviruses can also make cancer cells vulnerable to immunotherapy.

This project seeks to study the biology that connects this drug-resistant cancer cell state in lung cancer to the activation of these ERVs, and to use these insights to develop therapeutic strategies that enhance response to immunotherapy. Dr. Cañadas aims to perform genetic screens to identify regulators that control these ERVs in drug-resistant lung cancer cells. Ultimately, the use of a novel 3D culture technology using human lung cancer specimens will allow him to determine the most effective therapeutic combinations that promote responsiveness to immunotherapy. The proposed strategy addresses a key unmet need in the field in an effort to overcome resistance to immunotherapy due to intratumoral heterogeneity.