For example, erlotinib and lapatinib inhibited proliferation of all four tested cell lines, whereas gefitinib inhibited the proliferation of A1847 and SKOV 3 cells, and cetuximab inhibited the proliferation of OVCAR 7 and SKOV 3. Furthermore, subsets of T100 cells acquired de novo sensitivity to one or more of these FDA approved drugs IGROV 1 T100 cells and OVCAR 7 T100 cells acquired de novo www.selleckchem.com/products/arq-197.html sensitiv ity to gefitinib, and IGROV 1 T100 cells and A1847 T100 cells acquired de novo sensitivity to cetuximab. Discussion One assumption underlying the advent of personalized medicine has been the concept of assessing the molecu lar characteristics of a patients tumor in order to individ ually tailor a personalized treatment strategy.

Yet we and others clearly show that identification of a specific target molecule within a cell doesnt always correlate with suc cessful cell growth inhibition by biologically Inhibitors,Modulators,Libraries targeted therapeutics. Recent results across disease Inhibitors,Modulators,Libraries sites further suggest that it may be time to not only re evaluate the accuracy of target gene expression assays, but also the potential importance of target gene expression itself in forecasting responsiveness to certain biologically targeted therapeutics. The recent incongruity observed among EGFR expressing colon cancer patients and responsiveness to cetuximab is a case in point. In these studies, K Ras mutation status has proven to be a clinically useful negative indicator of responsiveness to cetuximab, but in no case is there a single accurate positive predictor of responsive ness to this new drug, including analysis of expression of cetuximabs target i.

e, EGFR, using currently available methods. K Ras, PTEN, c Met, and mutations in the EGFR tyrosine Inhibitors,Modulators,Libraries kinase domain, but not overall EGFR expression, are associated with resistance to Inhibitors,Modulators,Libraries EGFR tyrosine kinase inhibitors erlotinib and gefitinib in lung cancer, as reviewed in. More recently, Matulonis and colleagues demonstrated that tumor HER3 expres sion is a better predictor than HER2 for response to per tuzumab in patients with platinum resistant ovarian cancer. Even in the well studied case of breast cancer, Paik et al, have shown that patients with tumors expressing even low levels of HER2 may gain benefit from trastuzumab therapy. Together, these results are consistent with the notion that analysis of signaling networks and their aberrations may be better predictors of therapeutic response than is analysis Inhibitors,Modulators,Libraries of individual components within these networks.

In the case of EOC, for example, trastuzumab has not been shown to be effective in early clinical trials for the treatment of ovarian cancer patients. These disappoint ing results have been vexing since EOC tumors and EOC derived cell lines express or overexpress HER family members at the same frequency as do many malignant breast tumors. Yet, if http://www.selleckchem.com/products/brefeldin-a.html one examines the in vitro effects of trastuzumab, such results may be less surprising.