Finding biomarkers of resistance to targeted cancer therapies

In the past decade we have witnessed the emergence of a completely new class of cancer drugs: the targeted therapeutics. Such drugs are potentially far more powerful than the conventional broadly-acting chemotherapeutic agents as they target cancer-specific lesions. However, in spite of their often superior efficacy and limited toxicity, some of the old problems associated with the use of the previous generation of cancer drugs persist; most notably development of therapy resistance. Since these new drugs inhibit cancer-relevant signalling pathways in a highly specific fashion, only a limited number of genetic events may enable cancer cells to bypass such a specific block in proliferation. It is therefore likely that the molecular pathways that can cause resistance to such targeted therapies are similar in vitro and in vivo. Consequently, it should be possible to uncover mechanisms of resistance to targeted therapies in suitable pre-clinical models. In particular, unbiased genetic approaches in drug-sensitive cancer cell lines may be useful to identify candidate biomarkers of therapy resistance. Here I discuss the new genetic tools that have become available to perform such studies with an emphasis on the applications of these technologies to identify biomarkers of resistance to targeted therapies.