The U.S. National Cancer Institute (NCI) awarded a 5-year, $652,799 Project Grant (CFDA 93.396 - Cancer Biology Research) to the Fred Hutchinson Cancer Center (doing business as Seattle Cancer Care Alliance) to investigate the mechanisms and impact of "MAPK-driven kinetochore stress" in cancer cells. The research aims to reveal mechanistic details of this specific form of cellular stress, referred to as "MASKS", that arises from oncogenic signaling and destabilizes mitotic kinetochores in certain cancer types like glioblastoma. The award will fund three research objectives: (1) investigating the nature, function, and regulation of MASKS in glioblastoma samples; (2) determining the occurrence of MASKS in patient tumors; and (3) elucidating MASK-induced vulnerabilities in cancer and transformed cells. This work is expected to provide a direct mechanistic link between oncogenic RAS pathway signaling and chromosome instability in cancer, as well as identify potential biomarkers and therapeutic targets associated with the MASK phenomenon.
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