Nature Communications (Nov 2018)

Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy

  • Hao Geng,
  • Changhui Xue,
  • Janet Mendonca,
  • Xiao-Xin Sun,
  • Qiong Liu,
  • Patrick N. Reardon,
  • Yingxiao Chen,
  • Kendrick Qian,
  • Vivian Hua,
  • Alice Chen,
  • Freddy Pan,
  • Julia Yuan,
  • Sang Dang,
  • Tomasz M. Beer,
  • Mu-Shui Dai,
  • Sushant K. Kachhap,
  • David Z. Qian

DOI
https://doi.org/10.1038/s41467-018-07411-7
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 16

Abstract

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Prostate cancer often develops resistance to androgen receptor (AR) targeting drugs. Here, the authors show that, under conditions of hypoxia, AR inhibition via enzalutamide increases the expression of the glycolytic enzyme phosphoglucose isomerase (GPI) promoting a metabolic rewiring that allows the cells to survive, and consistent GPI inhibition restores sensitivity to enzalutamide.