Targeting lineage plasticity to suppress DTP in RET-positive lung cancer

Grant title (if any)
RETpositive / LUNGevity Foundation Lung Cancer Research Award
Hideo Watanabe, MD, PhD
Icahn School of Medicine at Mount Sinai
New York

Despite an initial response to the newly approved RET inhibiting drugs, most RET-positive lung cancers become resistant to these drugs and the cancers relapse. Dr. Watanabe’s project will provide anti-relapse therapeutic strategies for RET-positive lung cancer that target newly identified “drug-tolerant persisters (DTPs)”. DTPs are a small population of cancer cells that do not respond to these drugs and therefore start growing, leading to the relapse of these cancers. The role of DTPs in RET-positive lung cancer is not well understood. Dr. Watanabe proposes therapeutic strategies, such as targeting the Wnt and Hippo signaling pathway to overcome the DTP adaptability and prevent relapse before these cells arise.