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Can I read Targeting the PI3K/AKT pathway overcomes enzalutamide resistance by inhibiting induction of the glucocorticoid receptor on EtoBox?
Targeting the PI3K/AKT pathway overcomes enzalutamide resistance by inhibiting induction of the glucocorticoid receptor by Remi Adelaiye-Ogala; Berkley E. Gryder; Yen Thi Minh Nguyen; Aian Neil Alilin; Adlai R. Grayson; Wardah Bajwa; Keith H. Jansson; Michael L. Beshiri; Supreet Agarwal; Jose Antonio Rodriguez-Nieves; Brian Capaldo; Kathleen Kelly; David J. VanderWeele is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Targeting the PI3K/AKT pathway overcomes enzalutamide resistance by inhibiting induction of the glucocorticoid receptor about?
The PI3K-AKT pathway has pleiotropic effects and its inhibition has long been of interest in the management of prostate cancer, where a compensatory increase in PI3K signaling has been reported following androgen receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction of other hormone receptors, in particular the glucocorticoid receptor (GR). Here we demonstrate that AKT inhibition significantly decreases cell proliferation through both cytostatic and cytotoxic effects. The cytotoxic effect is enhanced by AR inhibition and is most pronounced in models that induce compensatory GR expression. AKT inhibition increases canonical AR activity and remodels the chromatin landscape, decreasing enhancer interaction at the GR gene () locus. Importantly, it blocks induction of GR expression and activity following AR blockade. This is confirmed in multiple models, where AKT inhibition of established xenografts leads to increased canonical AR activity, decreased GR expression, and marked antitumor activity. Overall, our results demonstrate that inhibition of the PI3K/AKT pathway can block GR activity and overcome GR-mediated resistance to AR-targeted therapy.
Who reads Targeting the PI3K/AKT pathway overcomes enzalutamide resistance by inhibiting induction of the glucocorticoid receptor?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Remi Adelaiye-Ogala; Berkley E. Gryder; Yen Thi Minh Nguyen; Aian Neil Alilin; Adlai R. Grayson; Wardah Bajwa; Keith H. Jansson; Michael L. Beshiri; Supreet Agarwal; Jose Antonio Rodriguez-Nieves; Brian Capaldo; Kathleen Kelly; David J. VanderWeele
- Publisher
- American Association for Cancer Research; American Association for Cancer Research (AACR) (ISSN 1535-7163)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)