Implication of heat shock protein 90 (HSP90) in tumor angiogenesis: a molecular target for anti-angiogenic therapy?
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Implication of heat shock protein 90 (HSP90) in tumor angiogenesis: a molecular target for anti-angiogenic therapy? / Staufer, Katharina; Stöltzing, Oliver.
In: CURR CANCER DRUG TAR, Vol. 10, No. 8, 8, 2010, p. 890-897.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Implication of heat shock protein 90 (HSP90) in tumor angiogenesis: a molecular target for anti-angiogenic therapy?
AU - Staufer, Katharina
AU - Stöltzing, Oliver
PY - 2010
Y1 - 2010
N2 - The inhibition of oncogenic signaling pathways has gained great interest for cancer therapy. In this context, the molecular chaperone heat shock protein 90 (HSP90) has emerged as a promising molecular target, since it is critically involved in maintaining stability, integrity and functions of key oncogenic proteins. A variety of HSP90 inhibitors have been developed in the past decade and have shown convincing anti-neoplastic activity in pre-clinical tumor models. Importantly, HSP90 inhibitors are predominantly being recognized as "tumor cell targeting" agents since cancer cells a) overexpress HSP90 protein, b) highly rely on HSP90 function for maintaining oncogenic signaling, and c) HSP90 inhibitors bind with high affinity to HSP90 in tumor cells. Nevertheless, results from recent studies also suggest that HSP90 inhibitors elicit anti-angiogenic properties by affecting the PI-3K/Akt/eNOS signal transduction pathway in endothelial cells, as well as through down-regulation of VEGFR-2 expression, a crucial component of the angiogenic process. In addition, blocking HSP90 may also diminish the secretion and expression of tumor cell-derived pro-angiogenic growth factors and cytokines, thus leading to "indirect" anti-angiogenic effects. This review article focuses on the role of HSP90 in angiogenesis and on delineating the effects of HSP90 inhibitors on angiogenic signaling pathways involved in tumor vascularization.
AB - The inhibition of oncogenic signaling pathways has gained great interest for cancer therapy. In this context, the molecular chaperone heat shock protein 90 (HSP90) has emerged as a promising molecular target, since it is critically involved in maintaining stability, integrity and functions of key oncogenic proteins. A variety of HSP90 inhibitors have been developed in the past decade and have shown convincing anti-neoplastic activity in pre-clinical tumor models. Importantly, HSP90 inhibitors are predominantly being recognized as "tumor cell targeting" agents since cancer cells a) overexpress HSP90 protein, b) highly rely on HSP90 function for maintaining oncogenic signaling, and c) HSP90 inhibitors bind with high affinity to HSP90 in tumor cells. Nevertheless, results from recent studies also suggest that HSP90 inhibitors elicit anti-angiogenic properties by affecting the PI-3K/Akt/eNOS signal transduction pathway in endothelial cells, as well as through down-regulation of VEGFR-2 expression, a crucial component of the angiogenic process. In addition, blocking HSP90 may also diminish the secretion and expression of tumor cell-derived pro-angiogenic growth factors and cytokines, thus leading to "indirect" anti-angiogenic effects. This review article focuses on the role of HSP90 in angiogenesis and on delineating the effects of HSP90 inhibitors on angiogenic signaling pathways involved in tumor vascularization.
M3 - SCORING: Zeitschriftenaufsatz
VL - 10
SP - 890
EP - 897
JO - CURR CANCER DRUG TAR
JF - CURR CANCER DRUG TAR
SN - 1568-0096
IS - 8
M1 - 8
ER -