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Genetic variants in the renin-angiotensin system predict response to bevacizumab in cancer patients

Diana Moreno-Muñoz1,2, Juan R de la Haba-Rodríguez1,2, Francisco Conde1,2

  • 1Oncology Department, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Reina Sofía, University of Córdoba, Córdoba, Spain.

European Journal of Clinical Investigation
|October 29, 2015
PubMed
Abstract

Insights

Genetic variations in the renin-angiotensin system (RAS) influence response to bevacizumab. Higher activity in the ACE-angiotensin-II-AGTR1 axis predicts better outcomes for anti-angiogenic cancer therapy.

Area of Science:

  • Oncology
  • Pharmacogenomics
  • Cardiovascular Research

Background:

  • Predictive biomarkers for anti-angiogenic cancer therapies are lacking.
  • Treatment response to anti-angiogenic drugs correlates with hypertension development.
  • Investigating genetic polymorphisms in the renin-angiotensin system (RAS) for predictive potential.

Purpose of the Study:

  • To explore the clinical relevance of genetic polymorphisms in RAS components.
  • To identify potential biomarkers for predicting response to bevacizumab therapy.
  • To assess the association between RAS gene variants and cancer patient outcomes.

Main Methods:

  • Genotyping of AGTR1-A1166C, AGT-M235T, and ACE I/D polymorphisms in 95 cancer patients treated with bevacizumab.
  • Analysis of circulating vascular endothelial growth factor and angiotensin converting enzyme (ACE) levels.
  • In vivo assessment of bevacizumab's antitumoral activity in AGTR1-overexpressing breast cancer models.

Main Results:

  • ACE IN/IN genotype associated with higher disease progression and shorter time to treatment failure.
  • AGTR1-1166A/A genotype linked to increased disease progression rates.
  • Higher circulating ACE levels correlated with better bevacizumab response.
  • Bevacizumab demonstrated enhanced antitumoral activity in AGTR1-overexpressing tumors.

Conclusions:

  • The ACE-angiotensin-II-AGTR1 axis activity is linked to improved bevacizumab response.
  • RAS genetic polymorphisms and activity may serve as predictive markers for anti-angiogenic drug efficacy.
  • This study supports the RAS as a valuable source for identifying predictive biomarkers in cancer therapy.
Keywords:
Angiogenesisangiotensinangiotensin II receptor 1breast cancercolorectal cancerpolymorphisms

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