The realization of the promise of personalized molecular medicine requires efficient development and implementation of novel targeted therapeutics linked to molecular markers able to identify patients most likely to benefit. An efficient integration of DNA, RNA and protein information content will be needed to identify patients likely to respond to particular therapies. The plethora of aberrations present in each tumor, the need to distinguish drivers from passengers, and the combinatorial effects of aberrations on critical cellular functions represent key challenges. The overall likelihood of response to therapy represents the interaction between predictors of sensitivity and predictors of resistance. Resistance can be pre-existing, adaptive, or acquired. Resistance can also occur through heterogeneity of molecular changes within the tumor and metastases. Adaptive resistance, which is the consequence of activation of homeostatic loops and phylogenetically conserved stress responses, provides a potential therapeutic liability that can be leveraged for rational combinatorial therapy. Thus a comprehensive analysis of patient tumors before, during and after treatment should become the standard of practice. Testing these precepts will require the development and implementation of novel trial designs. It is likely that we will need to increase the size of phase I and II trials to allow the identification and validation of molecular markers at the same time as the initial evaluation the toxicity and efficacy of targeted therapeutics. This will come with the advantage of much smaller phase III trials of patients selected for the likelihood to respond accelerating the approval of effective targeted therapeutics.
Medical Laboratory Technician33%
Manufacturer - Other33%