Le cancer broncho-pulmonaire sans mutation EGFR ni remaniement ALK-EML4 : vers de nouvelles cibles et de nouvelles thérapies ?

Some non-small cell lung cancers harbor single mutated oncogenes that, as EGFR mutation or ALK fusion genes, are valid predictors of increased sensitivity to specific inhibitors. Molecular subsets have been recently identified and are potential targets for new therapies. Thus, besides these two mutations, those illustrate the therapeutic relevance of molecular clusters, a lot of genomic alterations, belonging to the proteins of the MAPK family - as BRAF or MEK1 - or to the proteins of the PI3K signaling - as PI3KCA or AKT-have been found in lung tumors. However, because of the molecular complexity of NSCLC, the way from the identification of driver mutations to substantial therapeutic improvements will be certainly long. KRAS mutations are the most commonly mutated oncogenes and are essentially negative predictors of benefit from adjuvant chemotherapy or anti-EGFR therapy; inversely, no direct RAS inhibitors have proven clinically effective. Squamous-cell lung cancer do not benefit from these advances in targeted therapeutics, but the discovery of genome alterations, as amplifications of FGFR1 or mutations of the DDR2 gene, can be the first step for development of distinct molecularly therapeutics.