Federal Grant Award Summary

The National Cancer Institute awarded a $752,808 Project Grant to Sloan-Kettering Institute for Cancer Research under the Cancer Treatment Research program (CFDA 93.395) to conduct research on clonal hematopoiesis as a targetable mechanism of resistance to therapy in anaplastic thyroid cancer (ATC). The research project, spanning from June 1, 2026, through May 31, 2031, focuses on understanding how somatic mutations in blood-forming cells—particularly those affecting TET2 gene mutations—promote therapeutic resistance in ATC patients receiving BRAF and MEK inhibitors. The study employs syngeneic immunocompetent mouse models combined with single-cell RNA sequencing analysis to elucidate how mutant macrophages infiltrate tumors and confer resistance through TGF-beta signaling pathways.

The deliverables under this award include mechanistic research findings and preclinical evidence demonstrating that TGF-beta pathway inhibition at multiple nodes can restore sensitivity to MAPK pathway inhibition therapy. This research directly supports the Cancer Treatment Research program's objectives to develop improved cancer treatment methods and reduce treatment resistance, with particular relevance to elderly ATC patients who face dismal prognosis. The findings are expected to identify novel therapeutic targets and combination strategies that could improve patient outcomes beyond the current median overall survival of approximately 15 months.