New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances
Cet article passe en revue les perspectives offertes par une taxonomie génomique pour le traitement du mélanome métastatique
The discovery of BRAF and KIT mutations provided the first basis for a molecular classification of cutaneous melanoma on therapeutic grounds. As BRAF targeted therapy quickly moves towards regulatory approval and incorporation as standard therapy for patients with metastatic disease, proof of concept has also been established for targeting mutated KIT in melanoma. NRAS mutations have long been known to be present in a subset of melanomas and represent an elusive subgroup for targeted therapies. Matching patient subgroups defined by genetic aberrations in the PI3 kinase and p16/CDK4 pathways with appropriate targeted therapies has not yet been realized. And, an increasing understanding of lineage specific transcriptional regulators, most notably MITF, and how they may play a role in melanoma pathophysiology has provided another axis to approach with therapies. The foundation has been established for individual oncogene targeting and current investigations seek to understand the intersection of these susceptibilities and other described potential targets and pathways. The melanoma field stands poised to take the lead amongst cancer subtypes in advancing combination therapy strategies that simultaneously target multiple biologic underpinnings of the disease.