Project Grant R01CA316814

The National Cancer Institute awarded The Trustees of Columbia University in the City of New York $532,627 for research on tumor suppressive functions of SMARCA4 in lung cancer, effective September 1, 2026, under the Cancer Biology Research program (CFDA 93.396).

The award funds a five-year project (through August 31, 2031) conducted at Columbia's Health Sciences Division in New York, New York. The research develops and employs genetically engineered mouse models of SMARCA4-deficient lung adenocarcinoma to investigate how SMARCA4 alterations—present in approximately 10 percent of non-small cell lung cancer cases—drive disease progression and poor therapeutic response. The work tests the central hypotheses that SMARCA4 deficiency sustains inflammatory signaling that drives tumor progression and treatment resistance, and that targeting these inflammatory processes will restrain progression and improve therapeutic outcomes. In Aim 1, the investigator performs in vivo genetic inactivation of JAK-STAT pathway components in SMARCA4-deficient models to establish how JAK-STAT upregulation drives tumor progression; assesses tumor and immune phenotypes; evaluates the JAK-STAT pathway as a therapeutic target through preclinical studies of selective JAK1 inhibitors alone and in combination with immune checkpoint inhibitors; and characterizes patient samples for associated biomarkers. Aim 2 investigates how expression of the pro-inflammatory S100A9-S100A8 heterodimer in SMARCA4-deficient lung adenocarcinoma promotes disease progression. The project advances fundamental knowledge of cancer biology with the expectation of improving methods of prevention, detection, diagnosis, and treatment of lung cancer.