Looks like Casamento used options on Friday and hopefully moved them to his trust? Maybe Dr. M also used this method?
SGI-110 as a priming agent. Here is a piece from AACR:
We recently demonstrated for the first time in a clinical trial that therapeutic interventions targeting the OC methylome reverse drug resistance and induce meaningful clinical responses. While the FDA-approved demethylating agent decitabine is prone to deamination by cytidine deaminase, SGI-110 (Astex Pharmaceuticals, Inc.), a dinucleotide analogue of decitabine, is more stable, less toxic, and a promising alternative to restoring silenced TSG expression in cancer cells by reversal of DNA methylation
This may be a huge success for SGI-110 acting as a priming agent for hundreds of drug combinations. If you read the abstracts you hear words like Significant anti tumor response as describing sgi-110.
There's a case being made that SGI110 + CG Vaccinations in Myeloid Maligancies.
AT9283 +CNX652 in Non Hodgins Lymphoma.
AZD5363 In two presentations at AACR.Update in the Japan solid tumor trial.
AT-IAP I feel will be the next drug they take into trials.
Whomever buys this company out will be getting it at a steal. Watch this gap to $7 after AACR and looing for a $30 buyout. DR. M will not let it go cheaper.
Nice find Hate. Promising news coming out of AT13387 also it appears. You back back in or still holding the 35k freebies?
Abstract Number: 2433
Presentation Title: In vitro and in vivo antitumor activity of the next generation HSP90 inhibitor, AT13387, in both hormone-sensitive and castration-resistant prostate cancer models
Presentation Time: Tuesday, Apr 09, 2013, 8:00 AM -12:00 PM
Location: Hall A-C, Poster Section 4
Poster Board Number: 3
Author Block: Roberta Ferraldeschi1, Somaieh Hedayat1, Tomoko Smyth2, Nicola Wallis2, John Lyons2, Ruth Riisnaes1, Mateus Crespo1, Daniel Nava Rodrigues1, Susana Miranda1, Swee Sharp1, Gerhardt Attard1, Suzanne Eccles1, Paul Workman1, Johann de Bono1. 1The Institute of Cancer Research, United Kingdom; 2Astex Pharmaceuticals, United Kingdom
Abstract Body: HSP90 is a molecular chaperone involved in the conformational maturation and function of a large number of ‘client’ proteins that have been implicated in oncogenesis. The androgen receptor (AR), a key driver of prostate cancer growth and treatment resistance, is an HSP90 client and its function is dependent on HSP90 chaperone activity. The aim of this study was to evaluate the anti-tumour activity of AT13387, a novel second generation non-ansamycin HSP90 inhibitor, in prostate cancer models. AT13387 is currently being investigated in the clinic in GIST and NSCLC. It is a potent inhibitor of HSP90 (Kd 0.71 nM) and has previously been shown to inhibit proliferation and bring about the depletion of client proteins in a wide range of cell lines as well as inhibiting tumor growth in a number of xenograft models. In prostate cancer cell lines (VCaP, LNCaP, 22Rv1), AT13387 treatment depleted HSP90 clients such as AKT, HER-2 and CRAF, along with the induction of HSP72, confirming target inhibition. AT13387 treatment also resulted in depletion of mutant and wild-type AR, as well as the constitutively active truncated AR splice variant 7 (AR-V7). HSP90 inhibition disrupted AR nuclear localisation and AR transcriptional activity and resulted in down-regulation of AR-regulated genes in vitro. Inhibition of HSP90 translated into proliferative inhibition, with GI50 values in the range of 15-70 nM, and induction of apoptosis. AT13387 showed substantially greater potency than the first generation, natural product-based HSP90 inhibitor 17-AAG in modulating HSP90 client proteins, inhibiting cell growth and inducing cell death. The anti-tumor activity of AT13387 was demonstrated in vivo in a human xenograft model of castration-resistant prostate cancer. Our data suggest that HSP90 inhibition, through the use of more potent and better tolerated HSP90 inhibitors, will be active in multi drug resistant prostate cancer. These led to the design of a Phase I/II clinical trial of AT13387 with and without abiraterone acetate in castration-resistant prostate cancer no longer responding to abiraterone that is now accruing patients (NCT01685268).
KY, talking about Priming 'The results of clinical trials in lung cancer, led by Johns Hopkins’ Charles Rudin, M.D., and published late last year in Cancer Discovery, a journal of the American Association for Cancer Research, also indicate that the drugs AZA and DAC make tumors more responsive to standard anticancer drug treatment.
According to researchers, this means that the drugs could become part of a combined treatment approach rather than a standalone therapy and as part of personalized approaches in patients whose cancers fit specific epigenetic and genetic profiles."