Abstract
Combined radiation therapy with molecular targeting, which targets a specific molecule involved in tumor cell survival after irradiation, is one of promising approaches for improvement of tumor control. Because of tumor heterogeneity and the existence of multiple tumor radio-resistance pathways, an extension of this approach being investigated at the pre-clinical level is to use Hsp90 chaperone complex inhibitors as a means of reducing the levels of multiple radioresponse regulatory proteins. Hsp90 binds to multiple molecules that play an important role in malignant potential or determination of radiosensitivity of cancer cells, and stable binding between Hsp90 and these molecules (client proteins) is needed to maintain stability and function of client proteins. We have been investigating the effect of Hsp90 chaperone complex inhibition on radiosensitivity of several cancer cells, and confirmed synergistic enhancement of radiation-induced cell killing. In underlining mechanism for potentiation of radiation-induced cell killing, modification of several radioresponse regulatory proteins such as EGFR or Akt caused by Hsp90 chaperone complex inhibition was involved. In prostate cancer cells, Hsp90 inhibitor induced degradation of androgen receptor and downlegulation of prostate specific protein. Combined Hsp90 inhibitor with radiation caused synergistic enhancement effect of radiosensitivity of prostate cancer cells. In this conference, we report and discuss our results regarding the effect of Hsp90 chaperone complex inhibition on radiation-induced cell killing in cancer cells.
