Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The initiation of androgen deprivation therapy (ADT) induces susceptibilities in prostate cancer (PC) cells that make them vulnerable to synergistic treatment and enhanced cell death. Senescence results in cell cycle arrest, but cells remain viable. In this study, we investigated the mechanisms by which PC cells undergo senescence in response to ADT, and determined whether an FDA approved antidiabetic drug metformin has a synergistic effect with ADT in PC both in vitro and in vivo. Our results show that longer term exposure to ADT induced senescence associated with p16INK4a and/or p27kip2 induction. The activation of PI3K/Akt and inactivation of AMPK in senescent cells resulted in mTORC1 activation. In addition, the anti-apoptotic protein XIAP expression was increased in response to ADT. Addition of metformin following ADT induced apoptosis, attenuated mTOR activation by ADT, reduced senescent cell number in vitro and inhibited tumor growth in PC PDX models. This study suggests that combining ADT and metformin may be a feasible therapeutic approach to remove persistent PC cells after ADT.
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PMID:Synthetic Lethal Metabolic Targeting of Androgen Deprived Prostate Cancer Cells with Metformin. 3294 43


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