Chaithanya Vedula
Deciphering the Full Spectrum of Cellular Responses to KIF18A Inhibition
Abstract
Identifying common traits unique to cancer is crucial for the development of cancer-specific therapies. One trait is whole-genome doubling (WGD), an abnormal event where a cell duplicates its genome (WGD+ cell) and drives tumorigenesis in a striking 40% of cancers. Targeting WGD+ cells would impair cancer progression without damaging the normal diploid cells comprising the vast majority of the human body. We have shown that the mitotic kinesin KIF18A is nonessential for diploid cells, but becomes essential for WGD+ cell proliferation. This makes KIF18A an exciting target, as KIF18A inhibition (KIF18Ai) would kill WGD+ cancer cells without disrupting normal diploid cells, eliminating the side effects common to current chemotherapies. We aim to define the mechanisms governing KIF18Ai sensitivity and resistance, and assess the impact of KIF18Ai on the two proliferative WGD+ cell types existing normally in the body. This work will establish KIF18Ai as an essential first-line chemotherapy.
This award will allow me to advance research on a novel chemotherapy, with the hope of easing suffering and offering a brighter path forward for patients battling aggressive cancers.
