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RESEARCH PRODUCT

Targeted Therapies for Non-Small Cell Lung Cancer

subject

description

The discovery of new oncogenic driver mutations and the clinical development of targeted therapies have completely changed the paradigm treatment of non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib, ALK-inhibitors, crizotinib, and ceritinib, have been already approved for clinical use, benefiting many patients whose tumors harbor, respectively, EGFR or EML4-ALK molecular alterations. However, despite an initial benefit, tumor progression inevitably occurs, due to the development of acquired resistance to the targeted treatments. Several mechanisms of resistance have been identified, such as the secondary mutation of EGFR/EML4-ALK genes, or the activation of other oncogenic drivers. Several new compounds have been developed in order to overcome acquired resistance to first-generation TKIs, showing promising results in early phase I/II clinical trials, but further studies are needed to define their optimal role in the treatment algorithm of molecular selected NSCLC.