Moving from histological subtyping to molecular characterization: new treatment opportunities in advanced non-small-cell lung cancer.

Over the last 10 years, the systemic treatment of advanced non-small-cell lung cancer has progressively moved away from the 'one-size-fits-all' approach to histological subtyping. Currently, there is a progressive implementation of targeted therapies based on specific molecular characteristics such as the EGF receptor sensitizing mutations and the anaplastic lymphoma kinase rearrangements. Despite the availability of effective agents against these abnormalities, acquired resistance is still a major issue. A new generation of tyrosine kinase inhibitors for EGF receptor and anaplastic lymphoma kinase targeting acquired resistance mechanisms have been recently investigated. Several promising tyrosine kinase inhibitors that hit other targets are also in clinical development, including: rat sarcoma gene/MEK, BRAF1, PIK3A, c-mesenchymal-epithelial transition, c-ros oncogene 1, rearranged during transfection, human EGFR 2, FGFR, VEGFR, PDGFR and discoidin death receptor 2. Furthermore, new advances in immunology have been achieved through the discovery of vaccines and immune checkpoint pathways such as the cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1 and its ligands.