HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas. Issue 2 (1st September 2015)

• Record Type: Journal Article
• Authors: Ernst, Anne; Anders, Heike; Kapfhammer, Heidi; Orth, Michael; Hennel, Roman; Seidl, Karin; Winssinger, Nicolas; Belka, Claus; Unkel, Steffen; Lauber, Kirsten
• Is Part Of: Cancer letters. Volume 365:Issue 2(2015)
• Page Start: 211
• Page End: 222
• Publication Date: 2015-09-01
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.05.024
• Languages: English
• ISSNs: 0304-3835

Abstract

<abstract abstract-type="author-highlights" id="ab9010"> <title id="st9010">Highlights</title> <sec> <p id="sp9010"> <list id="ulist9010"> <list-item id="u9010"> <label></label> <p id="p9010">Intrinsic radioresistance of soft tissue sarcoma cell lines as measured by clonogenic survival varies substantially.</p> </list-item> <list-item id="u9015"> <label></label> <p id="p9015">Scores of radioresistance were extracted by principal component analysis of clonogenic survival data.</p> </list-item> <list-item id="u9020"> <label></label> <p id="p9020">mRNA levels of HSP90 and its clients ATR, ATM, and NBS1 reveal strong correlations with PCA-derived radioresistance scores.</p> </list-item> <list-item id="u9025"> <label></label> <p id="p9025">HSP90 inhibition preferentially sensitizes radioresistant sarcoma cells.</p> </list-item> <list-item id="u9030"> <label></label> <p id="p9030">Radiosensitization is accompanied by client protein degradation and delayed γ-H2AX foci clearance.</p> </list-item> <list-item id="u9035"> <label></label> <p id="p9035">HSP90 inhibitor concentrations sufficient for radiosensitization do not affect irradiation-induced apoptosis or necrosis.</p> </list-item> <list-item id="u9040"> <label></label> <p id="p9040">HSP90 inhibitor-mediated radiosensitization is accompanied by enforced basal and irradiation-induced senescence.</p> </list-item> <list-item id="u9045"> <label></label> <p id="p9045">Soft tissue sarcomas with particularly poor prognosis reveal elevated levels of HSP90, ATR, ATM, and NBS1.</p> </list-item> <list-item id="u9050"> <label></label> <p id="p9050">These aggressive soft tissue sarcomas might preferentially respond to HSP90 inhibition in combination with radiotherapy.</p> </list-item> </list> </p> </sec> </abstract>