Federal Grant Award Summary

The National Cancer Institute awarded a Project Grant of $681,818 to The Trustees of Columbia University in the City of New York (Health Sciences Division) under the Cancer Treatment Research program (CFDA 93.395) for the period June 2, 2026 through May 31, 2031. The research focuses on restoring anti-tumor immunity in chromosomally unstable tumors through investigation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) signaling pathway. The project will develop and evaluate small molecule cGAS inhibitors to counteract immune escape mechanisms driven by chromosomal instability in solid tumors, with the goal of sensitizing otherwise resistant cancers to immunotherapies including STING agonists and anti-PD1 checkpoint inhibitors.

The deliverables include rigorous preclinical research activities encompassing epistasis experiments, mechanistic studies of STING depletion and interferon tachyphylaxis, development of optimized small molecule cGAS inhibitors with favorable pharmacokinetic and safety profiles, and in vivo studies to establish the generalizability of findings across multiple cancer types. The research builds on preliminary data including human genomic analyses, tissue sampling studies, and animal models that demonstrate restoration of interferon-stimulated gene expression and improved immunotherapy responsiveness when cGAS signaling is inhibited. This translational research aims to provide a novel therapeutic approach to overcome immune evasion in chromosomally unstable cancers.