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Patients can be treated successfully with a combination of drugs
Advances in cancer therapy increasingly reflect the application of genomics and proteomics to target tumor-specific phenomena. Several insights have accelerated this process including the primacy cell survival signals in carcinogenesis and drug resistance and the growing appreciation of tumor biology as contextual.
Cell function analysis of programmed cell death addresses both issues by measuring metabolic and morphologic features of drug induced cell death (apoptotic and non-apoptotic) using native cultures isolated from surgical specimens and cytologically + fluids. The predictive validity of this functional profiling platform established for cytotoxics, has led to this platforms current focus on signal transduction. A cell "function" exploration of "vertical" and "horizontal" signal inhibition.
By expanding beyond current FDA-approved drugs into the new agents that target PI3K, AKT, TORC1&2, MEK/ERK and c-MET, functional profiling can facilitate developmental therapeutics. Analyses are now examining the activity and synergy of EGFR-TKIs with VEGF, mTOR, MEK/ERK, PI3K, AKT and c-MET inhibitors in various diseases.
There are lots of things that determine if drugs work, beyond the existence of a given target. Does the drug even get into the cancer cell? Does it get pumped out of the cell? Does the cell have ways of escaping drug effects? Can cells repair damage caused by the drug? Do combinations of drugs work in ways which can't be predicted on the basis of static gene expression patterns?
There are a number of drugs that could hold benefit for the patient with ovarian cancer and a number of novel combinations. Drugs are tested for activity both as single agents and in rational drug combinations, in order to assess possible drug synergies.
This involves using functional profiling analysis that allows for simultaneous identification of anti-tumor activity and anti-vascular activity in established anti-cancer drug treatments and also in novel combinations of standard drugs, kinase-inhibiting drugs and anti-angiogenesis agents.
Literature Citation:
Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007
Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)
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