Stay Away From
Each Of These
Resources Which Could Harm Any
MG132 For Good
Everolimus was generally well toler ated and safety findings were consistent with those from RECORD 1 and from a phase 1 study of everolimus in Chinese patients with advanced solid tumors. This study provides further evidence supporting the use of everolimus as a standard of care Stay Away From
Techniques Which May Destroy Any
PTC124 For Good in patients with VEGFr TKI refractory mRCC. Background In the United States, renal cell carcinoma is the seventh and ninth most common form of cancer in men and women, respectively, and a recent report estimates that in 2012, 40,250 men and 24,520 women will be diagnosed with, and 13,570 will die of, this disease. The therapeutic options for RCC have increased consi derably since 2005, due to the availability of seven new agents developed to interrupt the molecular path ways regulating tumor angiogenesis, cell proliferation, and survival.
Treatments of metastatic RCC with these agents, which are inhibitors of vascular endothelial growth factor, VEGF receptors, or mTOR, have a signifi cantly improved survival, but remain palliative. Thus, a cure for metastatic RCC continues to be elusive, but is being pursued actively with various combination strat egies. In this respect, it is noted that the time honored, but not regulatory approved, therapies with interferon alpha have had mixed results in RCC when used in combination with some of these agents. For example, IFN 2b combined with sorafenib achieved an overall response rate of 33% in patients with metastatic disease, IFN 2b combined with temsirolimus was not as ef fective as temsirolimus alone, and IFN combined with bevacizumab significantly increased progression free survival and objective responses.
One major challenge with IFN therapy, either alone or in combin ation, is the frequency with which IFN needs to be administered. Another problem associated with IFN therapy was the adverse events, which include fatigue, fever, nausea, flu like symptoms, and anorexia. While pegylated IFN has allowed for less frequent dosing, many of the same toxic effects remain without appreciable improvement in patient outcome. Inhibition of the mTOR kinase results in the reduction of regulatory proteins involved in the progression of cells from the G1 to S phase of their growth cycle. However, blocking mTOR activity with rapamycin or rapamycin analogs inadvertently acti vates the Akt signaling pathway through an IGF 1R dependent mechanism, which mitigates the anti tumor effects of the mTOR inhibitors. Thus, the combin ation of an anti IGF IR antibody with mTOR inhibitors was shown to block the Akt signaling pathway in rhabdo myosarcoma, breast, and prostate carcinomas, resulting in an additive increase in cell growth inhibition.