Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded the Regents of the University of Michigan a Project Grant totaling $444,775 (Award Date: June 1, 2026; Completion Date: April 30, 2031) under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the cardiotoxicity mechanisms of osimertinib and develop therapeutic interventions. The project will deliver research findings on how this kinase inhibitor—the sole approved therapy for EGFR T790M-positive non-small cell lung cancer—causes cardiac adverse effects in 3-5% of patients, including reduced left ventricular ejection function, heart failure, and arrhythmias that compromise cancer treatment continuity.

The research will produce mechanistic insights into osimertinib-induced cardiotoxicity through three specific aims: (1) elucidating mitochondrial mechanisms underlying cardiac injury using human-induced pluripotent stem cell-derived cardiomyocytes to measure mitochondrial function and reactive oxygen species levels; (2) assessing the role of NOX4 in mediating cardiac dysfunction; and (3) evaluating therapeutic strategies targeting mitochondrial dysfunction and oxidative stress. The deliverables will include peer-reviewed publications, data on mitochondrial bioenergetics disruption, and validated therapeutic targets to prevent treatment interruptions and improve patient outcomes in cancer therapy.