TY - JOUR
T1 - Anti-vascular therapies in ovarian cancer
T2 - moving beyond anti-VEGF approaches
AU - Choi, Hyun Jin
AU - Armaiz Pena, Guillermo N.
AU - Pradeep, Sunila
AU - Cho, Min Soon
AU - Coleman, Robert L.
AU - Sood, Anil K.
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Anti-vascular agent
KW - Ovarian cancer
KW - Resistance to anti-VEGF therapy
KW - Targeted therapy
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U2 - 10.1007/s10555-014-9538-9
DO - 10.1007/s10555-014-9538-9
M3 - Article
C2 - 25544368
AN - SCOPUS:84925457982
SN - 0167-7659
VL - 34
SP - 19
EP - 40
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 1
ER -