Prostate cancer heterogeneity: Discovering novel molecular targets for therapy

Cancer Treat Rev. 2017 Mar:54:68-73. doi: 10.1016/j.ctrv.2017.02.001. Epub 2017 Feb 11.

Abstract

Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies. In the future, the identification of driver mutations present at a specific stage of the disease, the classification PCa based on specific molecular alterations, and the selection of the most appropriate therapy based on biomarkers predictors of response represent the foundations for an increasingly more accurate personalized medicine.

Keywords: BRCA; CRPC; DRG; Heterogeneity; PARPi; PTEN; Prostate cancer.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • Humans
  • Male
  • Molecular Targeted Therapy / methods*
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Androgen / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • Receptors, Androgen
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human