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The yin yang of sunitinib: One drug, two doses, and multiple outcomes.
Our recent work showed that sunitinib exerts dual effect on cancer cells in different dose ranges. In clinically relevant doses, cancer cells tolerate sunitinb cytotoxicity by upregulating pro-survival MCL-1 and activating mTORC1 signaling. Inhibition of MCL-1 or mTORC1 sensitized cancer cells to sunitinib. Analysis of tissues from patients correlated MCL-1/mTORC1 induction with resistance to sunitinib.
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