Androgen Receptor

Treatment designed to block androgen receptor (AR) signaling in prostate cancer is the first known example of a "precision medicine" approach to cancer therapy that continues to be the major focus of treatment for advanced prostate cancer. A major focus of the lab has been the identification of down-stream ''effector'' genes that are responsible for cellular events (e.g. proliferation) after androgen receptor (AR) activation. We have identified a network of genes that are regulated by androgens in prostate cancer cells. Systematic studies involving the genetic and pharmacological modulation of these genes are designed to determine their cellular function with the aim of identifying those genes involved in proliferation, anti-apoptosis, differentiation, and treatment resistance. Genes with prostate-restricted expression serve as therapeutic targets for immunological and pharmacological strategies.

Questions and Projects

  • How do prostate cancers re-activate the AR program following AR antagonism?
  • What are the AR bypass pathways that maintain cell survival following AR ablation?
  • How do cells ‘transdifferentiate’ to assume new phenotypes following AR inhibition?
  • Can Supraphysiological levels of androgens repress prostate cancer growth? What are the mechanisms?
androgen receptor graphic
Recurrent molecular aberrations in metastatic prostate cancer include a high-frequency of androgen receptor amplification and gain-of-function mutations.


  • Nelson PS. Molecular States underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J. Clin Oncol. 2012 Feb 20;30(6):644-6. PMID: 22184375
  • Bluemn EG et al. Androgen Receptor Pathway-Independent Prostate Cancer is Sustained through FGF Signaling. Cancer Cell. 2017 Oct 9;32(4):474-489. PMID: 29017058.
  • Viswanathan SR et al. Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing. Cell. 2018 Jul 12;174(2):433-447. PMID: 29909985