In numerous tumor cells, heat shock protein 90 （Hsp90） is over-expressed and forms multi-chaperone complexes with client proteins that are involved in processes characteristic of malignant phenotypes, such as angiogenesis, invasion, and metastasis. Moreover, Hsp90 stabilizes several proteins such as Raf-1, Akt, ErbB2, and hypoxia-inducible factor 1α, which are known to be associated with protection against radiation-induced cell death. These findings suggest that Hsp90 inhibitors could be used in a multi-target-based approach to radio sensitize tumor cells. A number of studies have explored Hsp90 as a potential molecular target for sensitization of tumor cells after X-rays.
Some small studies have investigated the combined effects of Hsp90 inhibitors and high linear energy transfer carbon ion radiotherapy （C-ion RT）, a potential therapy against radio-resistant malignant tumors. In the case of aggressive malignant tumors, achieving a complete response to radiotherapy is difficult, which suggests that combination therapy might be necessary for such tumors. This review is to examine the effects of 17-llylamino-17-demethoxygeldanamycin （17-AAG, an Hsp90 inhibitor） based chemotherapy in combination with C-ion RT or X-rays on oral squamous cell carcinoma cells. 17-AAG and X-rays in combination showed enhanced antitumor effect compared to C-ion RT. The invasion cells significantly decreased after X-rays and C-ion RT, thus induced by irradiation showed dose-dependency for X-rays and C-ion RT. Moreover, when 17-AAG was added, X-rays and C-ion RT decreased invasion cells in an additive effect.
This review article describes the utility of combination therapy with an Hsp90 inhibitor and radiotherapy.
