Strategies to overcome drug resistance of receptor tyrosine kinaseaddicted cancer cells.

The use of agents capable of impairing RTK function is gaining prominence for their effectiveness against the tumorigenic program driven by oncogenic RTK activity in a wide range of cancer cells. Having this valuable resource in hand for molecularly targeted anticancer therapies, it is mandatory to understand how to use these agents properly for combined treatments in order to maximize clinical efficacy. The remarkable plasticity and adaptation of cancer cells should also be taken into account, since this leads to the acquisition of "resistance" during treatment. By revisiting mechanisms of drug resistance found in cancer cells and by intercalating new emerging concepts on RTK signaling coming from cancer genome studies, this review discusses strategies aimed to enhance the effectiveness of RTK blocking agents and overcome resistance to treatment.