Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

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• 作者：Hyun-Jin Choi (1)
  Guillermo N. Armaiz Pena (1)
  Sunila Pradeep (1)
  Min Soon Cho (4)
  Robert L. Coleman (1)
  Anil K. Sood (1) (2) (3)
  
  1. Department of Gynecologic Oncology and Reproductive Medicine Unit 1362 ; The University of Texas MD Anderson Cancer Center ; 1515 Holcombe Boulevard ; Houston ; TX ; 77030 ; USA
  4. Section of Benign Hematology ; Department of Pulmonary Medicine ; The University of Texas MD Anderson Cancer Center ; Houston ; TX ; USA
  2. Department of Cancer Biology ; The University of Texas MD Anderson Cancer Center ; Houston ; TX ; USA
  3. Center for RNA Interference and Non-Coding RNA ; The University of Texas MD Anderson Cancer Center ; Houston ; TX ; USA
  
• 关键词：Ovarian cancer ; Targeted therapy ; Angiogenesis ; Anti ; vascular agent ; Resistance to anti ; VEGF therapy
• 刊名：Cancer and Metastasis Reviews
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：34
• 期：1
• 页码：19-40
• 全文大小：508 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  
• 出版者：Springer Netherlands
• ISSN：1573-7233

文摘

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.