STA-9090 heat shock protein inhibitor Phase 1 Clinical Trial

[Bonni Hess]

Dear ASPS Community Friends,
My research has found a new clinical trial that may be effective when resistance is developed to tyrosince kinase inhibitors such as Sutent. The following is an excerpt from the Synta Pharmaceutical Company STA-9090 program overview with information about this promising new treatment:

About STA-9090
STA-9090 is a novel, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90), being developed for treating multiple solid tumor and hematologic cancers.

STA-9090 was discovered and developed internally at Synta and has a chemical structure unrelated to the first-generation, ansamycin family of Hsp90 inhibitors such as 17-AAG. In preclinical studies, STA-9090 has shown potency up to 100 times greater than the first-generation Hsp90 inhibitors as well as activity against a wider range of kinases. In in vitro and in vivo models, STA-9090 has shown potent activity against a wide range of cancer types, including lung, prostate, colon, breast, gastric, pancreatic, melanoma and certain hematologic cancers - as well as potent activity against cancers resistant to Gleevec, Sutent, Tarceva, Sprycel, and 17-AAG.

Mechanism of Action
STA-9090 potently inhibits Hsp90, a chaperone protein required for the proper folding and activation of other cellular proteins, particularly kinases. Many of these "client proteins" of Hsp90—such as AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, VEGFR—have been shown to be critical to cancer cell growth, proliferation, and survival and are the targets of clinically validated and approved cancer drugs such as Gleevec, Avastin, Herceptin, Sutent, Nexavar, Tarceva, and Erbitux. In preclinical studies, inhibiting Hsp90 causes the degradation of multiple client proteins and leads to cancer cell death. Because mutated kinases which no longer respond to treatment with kinase inhibitors remain dependent on Hsp90 for their activity, inhibiting Hsp90 offers the potential for treating cancers that have become resistant to targeted therapies such as kinase inhibitors. We believe that inhibiting kinases indirectly, by disrupting the chaperone activities of Hsp90, provides two advantages: first, a means to simultaneously attack multiple cancer-promoting kinases; and second, an ability to kill tumor cells with mutated kinases that have lost responsiveness to a direct kinase inhibit.

I will be following the treatment experience and results of a retroperitoneal sarcoma patient who is starting a Phase 1 Clinical Trial with this drug at Dana Farber, and I will keep this Board updated.
With special caring thoughts and continued Hope,
Bonni

[Arch]

Dear Bonni,

If the retroperitoneal sarcoma patient that you are following is Elsa, I happened to see her website http://livingwithasarcoma.blogspot.com/ and see that STA-9090 unfortunately was not very successful for her. If you have any other information about this trial, kindly let us know.

Arch

[Bonni Hess]

Dear Arch,
Yes, the retroperitoneal sarcoma patient who I am following through her livingwithsarcoma blog is Elsa, and yes, heartbreakingly the promising STA-9090 Clinical Trial was unsucessful in preventing the progression of her very challenging disease. Thank you for updating this thread with the information about the failed treatment results for her. I am not personally aware of any other sarcoma patients who have undergone treatment with this new drug, but I will continue to follow this Trial and wil post any new information that I find if and when it is available. Take care Arch.
With special caring thoughts and continued Hope,
Bonni