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Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic

Venessa T Chin1, Adnan M Nagrial1, Angela Chou1

  • 1The Kinghorn Cancer Centre,Cancer Division,Garvan Institute of Medical Research,384 Victoria St,Darlinghurst,Sydney,NSW 2010,Australia.

Expert Reviews in Molecular Medicine
|October 29, 2015
PubMed

Insights

Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors show promise in cancer therapy by normalizing tumor vasculature. Repurposing these agents may enhance chemotherapy and radiotherapy, improving patient outcomes.

Area of Science:

  • Oncology
  • Vascular Biology
  • Pharmacology

Background:

  • The Rho/ROCK pathway is crucial in cellular processes and a target in cancer medicine.
  • Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are clinically unproven for cancer but effective vasodilators.
  • ROCK inhibitors' role in cancer therapy requires further investigation.

Purpose of the Study:

  • To review the Rho/ROCK pathway's roles in angiogenesis, tumor vascular tone, and the tumor microenvironment.
  • To explore the potential of ROCK inhibitors as vascular normalizing agents in cancer treatment.
  • To assess the utility of ROCK inhibitors as adjuncts to standard cancer therapies.

Main Methods:

  • Literature review of the Rho/ROCK pathway in cancer.
  • Analysis of ROCK inhibitors' effects on tumor vasculature.
  • Exploration of ROCK inhibitors' potential to enhance chemotherapy and radiotherapy.

Main Results:

  • The Rho/ROCK pathway significantly influences angiogenesis and tumor vascular tone.
  • ROCK inhibitors demonstrate potential as vascular normalizing agents.
  • Pre-clinical studies show varied anti-cancer effects, but significant vasodilatory properties.

Conclusions:

  • ROCK inhibitors may improve chemotherapy and radiotherapy delivery and efficacy.
  • Repurposing ROCK inhibitors as adjuncts to standard treatments could enhance cancer patient outcomes.
  • Further understanding of Rho pathway regulation is key to clinical application of ROCK inhibitors in cancer.

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