Related Experiment Video

Updated: Mar 25, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.1K

P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer

Hira Lal Goel1, Bryan Pursell1, Leonard D Shultz2

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Cell Reports
|March 1, 2016
PubMed

Insights

Prostate cancer stem cells resist anti-VEGF therapies via VEGF/neuropilin signaling and P-Rex1 induction. Inhibiting Rac1 or P-Rex1 enhances treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Autocrine vascular endothelial growth factor (VEGF) signaling supports cancer stem cells (CSCs) in prostate and other cancers.
  • VEGF signaling is a validated therapeutic target for various cancers.

Purpose of the Study:

  • To investigate the mechanisms of resistance to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapies in prostate cancer stem cells (CSCs).
  • To identify novel therapeutic strategies to overcome resistance and improve treatment efficacy.

Main Methods:

  • Isolation and characterization of CSCs from prostate tumors and a PTEN(pc-/-) transgenic model.
  • Assessment of resistance mechanisms involving VEGF/neuropilin signaling, P-Rex1, Rac1, and ERK activation.
  • Evaluation of the effects of Rac1 inhibition and P-Rex1 downregulation on therapeutic sensitivity.

Main Results:

  • Prostate CSCs exhibit resistance to bevacizumab and sunitinib, mediated by VEGF/neuropilin signaling.
  • This resistance involves the induction of P-Rex1 (a Rac GEF) and subsequent Rac1-mediated ERK activation, dependent on Myc.
  • Rac1 inhibition or P-Rex1 downregulation sensitized prostate tumors to bevacizumab.

Conclusions:

  • Prostate tumors contain stem cell populations resistant to current VEGF/VEGFR-targeted therapies.
  • Combining VEGF/VEGFR inhibitors with P-Rex1 or Rac1 inhibitors could significantly improve therapeutic outcomes.

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.1K
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

11.8K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

1.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K