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- W4319294239 abstract "Abstract Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators that simultaneously modulate tumor immunity and another oncogenic pathway and then used it to identify 38 candidate immune–metabolic regulators. We show the tumor activities of these regulators stratify patients with melanoma by their response to anti–PD-1 using machine learning and deep neural approaches, which improve the predictive power of current biomarkers. The topmost identified regulator, ESRRA, is activated in immunotherapy-resistant tumors. Its inhibition killed tumors by suppressing energy metabolism and activating two immune mechanisms: (i) cytokine induction, causing proinflammatory macrophage polarization, and (ii) antigen-presentation stimulation, recruiting CD8+ T cells into tumors. We also demonstrate a wide utility of BipotentR by applying it to angiogenesis and growth suppressor evasion pathways. BipotentR (http://bipotentr.dfci.harvard.edu/) provides a resource for evaluating patient response and discovering drug targets that act simultaneously through multiple mechanisms. Significance: BipotentR presents resources for evaluating patient response and identifying targets for drugs that can kill tumors through multiple mechanisms concurrently. Inhibition of the topmost candidate target killed tumors by suppressing energy metabolism and effects on two immune mechanisms. This article is highlighted in the In This Issue feature, p. 517" @default.
- W4319294239 created "2023-02-07" @default.
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- W4319294239 date "2023-02-06" @default.
- W4319294239 modified "2023-10-06" @default.
- W4319294239 title "Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha" @default.
- W4319294239 cites W1107917109 @default.
- W4319294239 cites W1487322990 @default.
- W4319294239 cites W1597238753 @default.
- W4319294239 cites W1624269400 @default.
- W4319294239 cites W1904885158 @default.
- W4319294239 cites W1951724000 @default.
- W4319294239 cites W1966535852 @default.
- W4319294239 cites W1977453630 @default.
- W4319294239 cites W1979309473 @default.
- W4319294239 cites W1985987855 @default.
- W4319294239 cites W1989090840 @default.
- W4319294239 cites W2006617902 @default.
- W4319294239 cites W2026861011 @default.
- W4319294239 cites W2035618305 @default.
- W4319294239 cites W2040017417 @default.
- W4319294239 cites W2044141767 @default.
- W4319294239 cites W2050324752 @default.
- W4319294239 cites W2068046103 @default.
- W4319294239 cites W2100039832 @default.
- W4319294239 cites W2100122648 @default.
- W4319294239 cites W2102800926 @default.
- W4319294239 cites W2114652723 @default.
- W4319294239 cites W2117692326 @default.
- W4319294239 cites W2123830992 @default.
- W4319294239 cites W2123879591 @default.
- W4319294239 cites W2129205142 @default.
- W4319294239 cites W2130410032 @default.
- W4319294239 cites W2141102490 @default.
- W4319294239 cites W2141916112 @default.
- W4319294239 cites W2144508396 @default.
- W4319294239 cites W2156280702 @default.
- W4319294239 cites W2159707944 @default.
- W4319294239 cites W2178784291 @default.
- W4319294239 cites W2179438025 @default.
- W4319294239 cites W2252644942 @default.
- W4319294239 cites W2255621879 @default.
- W4319294239 cites W2271281302 @default.
- W4319294239 cites W2276479479 @default.
- W4319294239 cites W2293531514 @default.
- W4319294239 cites W2299181842 @default.
- W4319294239 cites W2309483848 @default.
- W4319294239 cites W2316870705 @default.
- W4319294239 cites W2329290504 @default.
- W4319294239 cites W2329768612 @default.
- W4319294239 cites W2330978860 @default.
- W4319294239 cites W2332292689 @default.
- W4319294239 cites W2495793061 @default.
- W4319294239 cites W2510597698 @default.
- W4319294239 cites W2530726117 @default.
- W4319294239 cites W2544405043 @default.
- W4319294239 cites W2559588208 @default.
- W4319294239 cites W2559849011 @default.
- W4319294239 cites W2579440183 @default.
- W4319294239 cites W2581073258 @default.
- W4319294239 cites W2581489880 @default.
- W4319294239 cites W2594575075 @default.
- W4319294239 cites W2594836176 @default.
- W4319294239 cites W2605152378 @default.
- W4319294239 cites W2605757478 @default.
- W4319294239 cites W2606711458 @default.
- W4319294239 cites W2610994169 @default.