Therapeutic targeting and monitoring tumor immunity in melanoma

There have been signi fi cant advances in melanoma therapy over the past several years, with several molecularly targeted and immunotherapeutic agents recently FDA-approved for use the treatment of patients with metastatic disease. Notable among these are inhibitors of the BRAF/MAPK pathway (targeted therapy), and antibodies that block immunomodulatory molecules on the surface of T cells and tumors (immune checkpoint inhibitors). However, with these advances, we are posed with therapeutic dilemmas with regard to timing and sequence of therapy. Namely, there is signi fi cant debate as to whether to begin treatment with targeted therapy versus immunotherapy upfront, and at which point to change treatment strategy. This is highly relevant, as each of these treatments as mono-therapy have signi fi cant limitations. focused fi effort on better understanding response and resistance to therapy through longitudinal tissue and blood analyses in patients on targeted therapy and to better understand molecular and immune mechanisms have critical insights which have led to therapeutic for patients with melanoma 2). This includes the use of combination strategies, such as adding immune checkpoint blockade to a backbone molecularly targeted with melanoma these and response data are not yet that complexities exist with regard to these combinations. A of and resistance to combination strategies through translational research is critical, is best performed on longitudinal patient samples during the course which may (and be informed by) approaches combining molecularly targeted and will be built on a deep understanding of the molecular and immune effects of each these therapies in isolation, well