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Updated: May 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

MET and VEGF: synergistic targets in castration-resistant prostate cancer

D T Aftab1, D M McDonald

  • 1Exelixis, Inc., South San Francisco, CA 94083-0511, USA. daftab@exelixis.com

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|October 7, 2011
PubMed

Insights

New prostate cancer treatments targeting angiogenesis show promise but face resistance. Combining MET and VEGF pathway inhibition may improve overall survival in castration-resistant prostate cancer with bone metastasis.

Area of Science:

  • Oncology
  • Cancer Research
  • Molecular Biology

Background:

  • Prostate cancer treatment has advanced, yet castration-resistant disease with bone metastasis requires novel therapeutic strategies.
  • Antiangiogenic agents targeting vascular endothelial growth factor (VEGF) signaling show activity but limited overall survival benefits in clinical trials.
  • Evasive resistance, potentially mediated by hepatocyte growth factor receptor (MET) signaling, may explain the suboptimal overall survival outcomes.

Purpose of the Study:

  • To explore the potential of combined MET and VEGF pathway inhibition for treating castration-resistant prostate cancer.
  • To investigate the role of MET signaling in angiogenesis, invasion, and bone metastasis in prostate cancer.
  • To enhance the efficacy of antiangiogenic therapies in advanced prostate cancer.

Main Methods:

  • Review of preclinical models and clinical biomarker studies on antiangiogenic agents.
  • Analysis of data from pivotal prostate cancer trials involving VEGF-targeting agents.
  • Examination of recent preclinical findings on MET pathway activation and its implications.

Main Results:

  • VEGF pathway inhibition improved tumor response and progression-free survival but not overall survival.
  • Preclinical data suggest MET signaling upregulation contributes to resistance against antiangiogenic therapy.
  • MET signaling is implicated in key castration-resistant prostate cancer processes like angiogenesis, invasion, and bone metastasis.

Conclusions:

  • Dual inhibition of MET and VEGF pathways presents a promising strategy to overcome resistance and improve outcomes.
  • Targeting MET signaling alongside angiogenesis may enhance the effectiveness of current treatments for advanced prostate cancer.
  • Further investigation into combined MET and VEGF pathway blockade is warranted for castration-resistant prostate cancer patients.

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