Inhibition of kinase HASPIN as a novel anti-tumor strategy to radiosensitize and boost the in situ vaccination effect of radiation 9073

Abstract Description Radiation therapy (RT) is a treatment used in roughly half of all cancer patients at some point over the course of their care. RT induces DNA damage that can kill cells if not properly repaired. DNA damaged by RT may also leak into the cytoplasm where it can be sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS) which activates Stimulator of Interferon Genes (STING) through a secondary messenger, cGAMP. STING activation induces the expression of pro-inflammatory genes that can potentiate the antitumor effect of RT. HASPIN is an understudied, atypical kinase involved in cell cycle progression and DNA repair; this kinase is frequently overexpressed in human cancers. Inhibition of HASPIN results in mitotic errors and DNA stress. We hypothesize that HASPIN inhibitors will work synergistically with RT to both radiosensitize the tumor and activate the cGAS/STING pathway. This novel treatment combination may result in a new strategy to augment the benefits of RT for treating cancer. Funding Sources Cancer Prevention and Research Institute of Texas, RP180725 (PI: Raquibul Hannan) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)