Results need to be confirmed in in vivo models and ultimately in human clinical trials. Recent interesting data has demonstrated that cisplatin binds to the C ROCK Kinase terminus of Hsp90 and interferes with nucleotide binding . Rosenhagen have demonstrated degradation of several steroid receptors, such as the androgen receptor, but not other client proteins, suggesting that it specifically inhibits steroid receptor Hsp90 complexes, although the exact mechanism by which this occurs remains to be elucidated. Similarly, the active component found in green tea, epigallocatechin3Gallate, has also been found to bind to the C terminus of Hsp90, but at doses studied does not appear to inhibit Hsp90 from forming its heteroprotein complexes .
Despite, this, the fact that several agents useful in treating cancer and hypothesized to be cancer preventative bind to the C terminus of Hsp90 is intriguing and deserves further study.cancer cells. Its interaction with a large number of proteins involved in the six different hallmarks of cancer make it an interesting and viable drug target for anticancer Pemetrexed therapies. The Nterminal inhibitors that have been tested to date in clinical trials have unfortunately had somewhat disappointing results. However, this may be due to the pharmacodynamic and pharmacokinetic properties of these agents, which may potentially be improved. In fact, several agents are in clinical trials that indeed possess improved properties in this regard. A number of large pharmaceutical companies have now entered into the field of Hsp90 inhibitors and may be able to provide improved profiles of these agents.
Also, combination therapy with traditional cytotoxic agents appears to offer improved efficacy eukaryotic yet acceptable toxicity. Interesting in vitro and in vivo data suggest that Hsp90 inhibitors may also increase radiosensitivity of several tumors and early trials are being planned. In addition, there remains much about Hsp90 that is just now being discovered, particularly with regard to its middle domain and C terminus. Increasing reports have identified inhibitors of the C terminus of Hsp90 and future in vitro and in vivo studies will determine if these agents can be used clinically, although, preliminary results appear very promising. Due to its involvement in so many pathways critical to cancer, and our elementary understanding of this unique molecular chaperone, Hsp90 remains a viable target for anticancer drug therapies and deserves greater study and investment in its development.
Heatshock protein 90 is a proangiogenic factor in mammalian tissues and in tumors; therefore, Hsp90 inhibitors were developed as antiangiogenic factors. In this study, we evaluated the association between Hsp90, hypoxia, and angiogenesis in the chick growth plate. Administration of the Hsp90 inhibitor to TD and ricketsafflicted chicks at the time of induction resulted in reduction in growthplate size and, contrary to its antiangiogenic effect in tumors, a major invasion of blood vessels occurred in the growth plates. This was the result of upregulation of the VEGF receptor Flk1, the major ratelimiting factor of vascularization in TD and rickets. In addition, the abnormal chondrocyte differentiation, as characterized by collagen type II expression and alkaline phosphatase .