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[Molecular genetic mechanisms of drug resistance in prostate cancer]

G S Krasnov1,2,3,4, A A Dmitriev1,2, A F Sadritdinova1

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.

Molekuliarnaia Biologiia
|October 30, 2015
PubMed

Insights

Prostate cancer treatment faces challenges with drug resistance, including cross-resistance. This review covers androgen-dependent and independent mechanisms, focusing on androgen receptor mutations and altered androgen synthesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer treatment frequently encounters drug resistance, a significant clinical challenge.
  • Cross-resistance, where resistance to one drug confers resistance to others, is particularly problematic.
  • Understanding resistance mechanisms is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To review the mechanisms underlying drug resistance in prostate cancer.
  • To differentiate between ligand-dependent and ligand-independent resistance pathways.
  • To highlight key molecular alterations contributing to treatment failure.

Main Methods:

  • Literature review of studies on prostate cancer drug resistance.
  • Analysis of mechanisms involving the androgen receptor (AR).
  • Examination of androgen synthesis pathways and their role in resistance.

Main Results:

  • Drug resistance in prostate cancer involves both androgen-dependent and independent mechanisms.
  • Key mechanisms include mutations in the androgen receptor and expression of splice variants.
  • Upregulation of genes involved in androgen synthesis also contributes to resistance.

Conclusions:

  • Androgen receptor alterations and dysregulated androgen synthesis are central to prostate cancer drug resistance.
  • Targeting these mechanisms may offer new therapeutic avenues.
  • Further research into resistance pathways is essential for improving patient outcomes.
Keywords:
abirateroneandrogen receptorandrogensdrug resistanceenzalutamidemutationsprostate cancersplice variants

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