Biological prognostic and predictive factors in lung cancer

The inclusion of new drugs in clinical research and practice has allowed improvements in several outcomes of advanced non-small-cell lung cancer (NSCLC). Among these drugs, very interesting results have been obtained from pemetrexed and new targeted agents, including the inhibitors of epidermal growth factor receptor (EGFR) such as gefitinib, erlotinib and cetuximab. Unfortunately, these new drugs when investigated for the treatment of small-cell lung cancer (SCLC) reported negative results. The results of these investigations seem to be related to specific factors that could indicate which patients could benefit from each specific therapy. Therefore, several clinical and biological factors might find use as prognostic or predictive markers. A prognostic factor provides information on outcome, independent of the therapy that is used. In contrast, a predictive factor provides information on outcome with regard to a specific therapy. Some factors, such as EGFR mutations, are both prognostic and predictive. In the present paper, we review data related to thymidylate synthase, EGFR and K-ras mutations, the most important biologic prognostic and/or predictive factors related to pemetrexed, gefitinib, erlotinib and cetuximab therapy in the treatment of advanced NSCLC and in SCLC patients.