**7. Conclusion**

74 Advances in the Biology, Imaging and Therapies for Glioblastoma

TMZ-treated cells. Isobologram analyses revealed that the interactions between 17-AAG and cisplatin or BCNU were synergistic, whereas the interaction between 17-AAG and TMZ was

The FACS analyses revealed that the population of cells with a sub-G1 DNA content was increased by combined treatment with 17-AAG and either cisplatin or BCNU; furthermore, the combined treatment remarkably increased the number of annexin V–positive and PInegative cells. These results demonstrated that the 17-AAG– induced enhancement of the DNA crosslinking agents–induced cytotoxicity was either associated in part or entirely with

Fig. 9. Effect of Hsp90 inhibitor 17-AAG on cytotoxicity induced by various DNA damaging

A reasonable concern is that hsp90 inhibitors may act not only on tumor cells, but also on normal cells; however, the authors of previous studies have shown that hsp90 is expressed at 2–10-fold higher levels in tumor than in normal tissue, and that hsp90 derived from

no more than additive (Figure 9).

an increase in apoptotic cell death.

agents.

We reviewed our studies focusing chemosensitization of gliomas. We propose that combination of conventional chemotherapy using DNA-damaging agents and molecular targeted therapy could be a potentially useful new antiglioma therapeutic strategy. However, enhancement of the effect of chemotherapeutic agents clearly depends on the mechanism by these compounds exhibit cytotoxicity. Therefore the development of a safe and effective therapeutic regimen will require further investigation
