The antiproliferative effects from the Akt inhibitor perifosine is improved when mixed with nanoparticle-bound rapamycin on multiple myeloma cells . Treatment of vemurafenib-resistant BRAF-mutant colorectal cancer cells with an Akt inhibitor overcame their resistance to vemurafenib . Heat shock inhibitors like the HSP90 inhibitor XL888, have already been proven to inhibit proliferation of some vemurafenibresistant melanoma cells . XL888 enhanced proapoptotic Bim expression and decreased Mcl-1 expression. Also decreases in PDGFR-beta, COT, IGF-1R, Raf-1, A-Raf, S6, cyclin D1 and Akt were observed. This result in nuclear accumulation of FOXO3a and resulted in expression within the proapoptotic Bim protein. Clinical Trials Based upon Inhibiting each the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Pathways. Combinations of Raf and PI3K/mTOR or MEK and PI3K/mTOR inhibitors are in clinical trials.
The results of a phase one clinical trial on sufferers with state-of-the-art solid tumors indicate the mixed dosing seems to become very well tolerated, no less than as well as single agent dosing. Some anti-tumor results have been observed and dose-escalation trials have been performed . NCT01138085 MG-132 is known as a clinical trial combining MEK and Akt inhibitors . NCT01347866 can be a clinical trial for individuals with advanced cancers combining the PI3K/mTOR inhibitors together with the MEK inhibitor or irinotecan. The study will include sufferers with metastatic CRC who have obtained previous therapy for his or her disorder and whose cancers have a mutant KRAS gene. The dual PI3K/mTOR inhibitor NVP-BEZ235 is inside a blend clinical trial with RAD001 in patients with innovative solid cancers. A phase one clinical trial is in progress combining the MEK1/2 inhibitor MEK162 and the PI3K/mTOR dual inhibitor NVP-BEZ-235.
This combination will be evaluated in many different cancer sufferers, for instance in NSCLC patients containing mutations at EGFR who’ve progressed following therapy with EGFR inhibitors or with individuals with triple Kinetin damaging breast, CRC, melanoma, and pancreatic cancers. Also, patients with other advanced sound tumors with KRAS, NRAS, and/or BRAF mutations might be incorporated in this trial. NCT01390818 is known as a analysis trial testing a blend of two experimental drugs, MSC1936369B and SAR245409 , for your treatment method of locally state-of-the-art or metastatic sound tumors. Individuals with breast, NSCLC, melanoma and colorectal cancers will likely be treated with this inhibitor combination. A clinical trial NCT01021748 is examining the effects of combining MK2206 and AZD6244 in cancer sufferers with advanced sound tumors.
NCT01519427 is really a clinical trial combining the MEK inhibitor selumetinib as well as Akt inhibitor MK2206 in patients with stage III or stage IV melanoma that previously failed following therapy with vemurafenib or dabrafenib.