alexa Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia.
Oncology

Oncology

Journal of Oncology Translational Research

Author(s): Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H, , Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H,

Abstract Share this page

Abstract Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenografts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. In vitro studies revealed that hypoxia-driven stem/progenitor cell enrichment is primarily mediated by hypoxia-inducible factor 1α. We further show that the Akt/β-catenin cancer stem cell regulatory pathway is activated in breast cancer cells under hypoxic conditions in vitro and in sunitinib-treated mouse xenografts. These studies demonstrate that hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs.
This article was published in Proc Natl Acad Sci U S A and referenced in Journal of Oncology Translational Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • Global Experts meeting on Oncology Case Reports
    Aug 29-31, 2017 London, UK
  • 25th World Congress on Cancer Science and Therapy
    October 18-20, 2017 Baltimore, Maryland, USA
  • 25th World Cancer Conference
    Oct 19-21, 2017 Rome, Italy
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords