Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches. Cancer Metastasis Rev 2015 Mar;34(1):19-40
Date
12/30/2014Pubmed ID
25544368Pubmed Central ID
PMC4369424DOI
10.1007/s10555-014-9538-9Scopus ID
2-s2.0-84925457982 (requires institutional sign-in at Scopus site) 82 CitationsAbstract
Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by anti-angiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies.
Author List
Choi HJ, Armaiz Pena GN, Pradeep S, Cho MS, Coleman RL, Sood AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAntineoplastic Agents
Female
Humans
Neovascularization, Pathologic
Ovarian Neoplasms
Protein Kinase Inhibitors
Signal Transduction
Treatment Outcome
Vascular Endothelial Growth Factor A
