Related Experiment Video

Updated: Jan 28, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer

Nicholas G Nickols1,2,3, Ramin Nazarian4, Shuang G Zhao5

  • 1Department of Radiation Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA.

Prostate Cancer and Prostatic Diseases
|February 27, 2019
PubMed
Abstract

Insights

Targeting the MEK/ERK pathway with trametinib shows promise for treating metastatic castration-resistant prostate cancer (mCRPC) when other treatments fail. This approach may offer a new therapeutic strategy for refractory mCRPC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive, incurable malignancy.
  • Treatment resistance to androgen receptor-signaling axis inhibitors is common in mCRPC.
  • There is a critical need for novel therapeutic strategies beyond hormonal manipulation for mCRPC.

Purpose of the Study:

  • To identify activated kinases as potential therapeutic targets in mCRPC.
  • To evaluate existing approved drugs for rapid translation into clinical trials for mCRPC.
  • To investigate the role of the MAPK pathway in prostate cancer progression.

Main Methods:

  • Compared mRNA expression in metastatic mCRPC biopsies (n=101) to localized prostate cancer from TCGA.
  • Inferred differential kinase activity based on transcriptomic profiling.
  • Assessed differential phosphorylation of key MAPK pathway kinases.

Main Results:

  • Hyperactive ERK1 and MAPK pathway amplifications (32%) identified in mCRPC.
  • Elevated phosphorylated ERK1/2 levels confirmed in castration-resistant vs. primary prostate cancer.
  • Phosphorylated ERK1/2 in primary tumors associated with biochemical failure post-prostatectomy.
  • Trametinib (MEK1/2 inhibitor) showed significant response in a heavily pre-treated mCRPC patient.

Conclusions:

  • Pharmacologic targeting of the MEK/ERK pathway is a potential treatment strategy for refractory mCRPC.
  • The MEK/ERK pathway represents a druggable target for mCRPC.
  • Clinical trials are underway to validate MEK/ERK pathway inhibition in mCRPC.

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