given the improved physiological profile of IPI 504 and its increased security, IPI 504 has been advanced to Phase I and II clinical trials for numerous cancers, including non-small cell lung cancer, gastrointestinal stromal cyst, multiple myeloma, castration resistant prostate cancer, and breast cancer. Non Small Cell Lung Cancer?EGFR is just a tyrosine Ganetespib clinical trial kinase receptor, it is also an Hsp90 client protein, and is often mutated in non small cell lung cancer. Phase I clinical trials of IPI 504 treatment of NSCLC involved 9 patients with known EGFR versions. Following a four week, twice weekly therapy with IPI 504, 7 of the patients had no new tumors appearing and small change in how big is tumors which were already present. Digestion IPI 504 was then advanced level to Phase II clinical trials for 10 patients with stage IIIB or known EGFR versions and IV NSCLC. This trial proved successful with 1 out-of 10 patients having a complete remission. This positive effect led to an expansion of the clinical trials with an individual populace of 57 patients with either EGFR mutant, wild type, or unknown term. Even though over all response rate to IPI 504 with these 3 different patient populations was 7%, the response rate of the individuals with only wild-type EGFR was 14. 2%. Further, this 14. 14 days demonstrated a cyst progression free period of 3. 9 months. With this promising data, IPI 504 was advanced to Phase III clinical trials. However, Infinity Pharmaceuticals recently ceased the tests when a review of the 46 patients enrolled in the study showed a greater mortality rate among patients treated with IPI 504 than those receiving a placebo. Myeloma?Against multiple myeloma cells, IPI 504 turned out to be a powerful Hsp90 inhibitor, disrupting most of the functions. These effects include suppression of cell surface expression CX-4945 ic50 and signaling for receptors associated with Hsp90, particularly IL 6 and IGF 1, reduced intracellular levels of many kinases, and finally tumor cell sensitization to other pro apoptotic drugs. Hsp90 inhibition is exclusive in MM cells when compared with other cancer cells since the consumer proteins that are inhibited are part of an unfolded protein response pathway. That pathway promotes cell survival by preventing the accumulation of misfolded proteins within the cell. Specific Hsp90 customer proteins associated with this pathway contain PERK/eIF 2, XBP 1, and ATF6. Preventing these customer proteins from binding to Hsp90 allows misfolded proteins to amass and causes apoptosis. Therapy of MM cells with IPI 504 indeed stops these client proteins from interacting with Hsp90, thereby curbing UPR, and inducing apoptosis. Hence, it appears that IPI 504 is a promising therapy for myeloma, where the UPR pathway is active. Prostate?In individuals with castration resistant prostate cancer Hsp90 customer proteins AR, Akt, and Her 2 are up regulated.
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