2015 Lung Cancer Research Foundation Annual Grant Program
Ralph Weichselbaum, MD
The University of Chicago
Research Project:
Radioinducible RNAs in the treatment of lung cancer
Summary:
An important limitation in the therapy of lung cancer is intrinsic and/or acquired resistance to radiotherapy and chemotherapy. However, mechanisms of resistance are poorly understood. Recently Dr. Weichselbaum’s team and others reported that Type 1 interferon signaling is required for optimal effects of cytotoxic therapies. Paradoxically, long term interferon signaling mediates resistance to cytotoxic agents. Work in Dr. Weichselbaum’s laboratory has demonstrated that cytotoxic therapies for lung cancer activate Type I IFN signaling through induction of small non-coding RNAs. The team is currently characterizing the origin and mechanism of activation/induction of specific small RNAs following genotoxic stress. Results from these experiments will identify new molecular pathways of chemo and radioresistance and novel targets for treatment strategies combining cytotoxic treatments. Both small RNAs and interferon are immunogenic, and they hypothesize that their results will help to understand potential beneficial combinations of immunotherapies and cytotoxins in lung cancer.