Biomarkers Predicting for Response and Relapse with Melanoma Systemic Therapy

Introduction of new systemic therapies in the last 10 years has radically improved outcomes for melanoma patients. Even so, not all patients benefit, so getting the right treatment to the right patient is a priority. These two major drug classes, small molecule targeted kinase inhibitors and immune check-point inhibitors, both come at significant cost, with sometimes serious side effects as well as high expense for health services. Almost half of melanomas harbour a >BRAF>V600 mutation and virtually all patients receiving BRAF targeted therapy will experience some amount of response. However, duration of response with these agents is uncertain, due to acquired resistance, which means few patients remain in response long term. Most metastatic melanoma patients are potentially eligible for immune checkpoint inhibitors, irrespective of BRAF status. However, only about half of patients will respond to these agents, and only half again will benefit long term. Thus, both primary and acquired resistance limit response. In this era of personalized anti-cancer therapy, biomarkers offer a means to predict for both response and relapse to a particular treatment. To date, the only validated bio-marker applied to selecting melanoma systemic therapy is the >BRAF gene. However, modern technologies are now opening up a wide range of candidate genes, polypeptides and proteins which are being evaluated for their potential clinical application as predictive biomarkers of the future.