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.