XZ carried out the fluorescence microscopy and Western blot studies and prepared cells for the multispectral imaging studies. XL performed Western blot and Rho pull-down assays. PJM participated in the design of the multispectral imaging studies, BEH did technical work for the multispectral imaging studies, and both PJM and BEH helped to analyze the data. WAW helped with

the interpretation of data and critical revision of the manuscript. All authors read and approved the final manuscript.”
“Introduction The increasing amount of knowledge about biological targets is nowadays going to switch the balancing and equilibrium between the medicine for the ‘entire population’ and the medicine for ‘the individual’, in favour Alisertib molecular weight Selleck SB273005 of the latter, in order to better aim to a modern concept of ‘ideal medicine’. The results obtained with the traditional clinical trial design with molecularly targeted agents so far are far from being optimal. Indeed, with the exception

of trastuzumab for breast cancer, we observe 4 common outcome patterns of randomized trials in solid BKM120 cell line tumors: 1) studies reporting a significant while small survival benefit for the targeted agent (advanced pretreated non-small-cell lung cancer, NSCLC, erlotinib versus placebo) [1]; 2) studies reporting a significant while minimal survival benefit for the targeted agent (advanced untreated pancreatic adenocarcinoma, erlotinib plus gemcitabine versus gemcitabine) [2]; 3) studies reporting no significant differences in survival (advanced pretreated NSCLC, gefitinib

versus placebo) [3]; and 4) studies reporting an unexpected significantly detrimental effect of the targeted agent (locally advanced NSCLC, maintenance Montelukast Sodium gefinitib after chemotherapy versus placebo) [4]. Given these scenarios, no major differences in the trials results with (old) and so-considered ‘un-targeted’ chemotherapeutics do appear, with the exception of trastuzumab. Targeted versus untargeted design for new drugs What is wrong with this design approach when molecularly targeted agents are tested? The ‘new age’ of medical oncology is experiencing many biological advances and discoveries from the basic science side and the new available techniques, concurrently with the release of new available drugs. Moreover, medical oncology represents the field of clinical medicine with the higher failure-rate for late-stage clinical trials, when compared to the other specialties, and with the higher time- and resource-intensive process, with more than 800 million US dollars to bring a new drug to market. So, the clinical trial design methodology needs to be updated, given the ‘confusion’ provided by the discovery of new targets, which identify (in many cases) new patient’ subgroups.