Article
Targeting the mevalonate pathway suppresses ARID1A-inactivated cancers by promoting pyroptosis.
Cancer cell - 10 Apr 2023
Zhou Wei, Liu Heng, Yuan Zhe, Zundell Joseph, Towers Martina, Lin Jianhuang, Lombardi Simona, Nie Hao, Murphy Brennah, Yang Tyler, Wang Chen, Liao Liping, Goldman Aaron R, Kannan Toshitha, Kossenkov Andrew V, Drapkin Ronny, Montaner Luis J, Claiborne Daniel T, Zhang Nan, Wu Shuai, Zhang Rugang
Abstract excerpt
ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and...
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