Molecular targeted therapy for patients with melanoma: the promise of MAPK pathway inhibition and beyond.

IMPORTANCE OF THE FIELD: Recent discoveries have expanded the understanding of the molecular signaling events critical to melanomagenesis and led to the development of targeted therapeutic agents that are revolutionizing the treatment of patients with advanced melanoma. AREAS COVERED IN THIS REVIEW: This article reviews current therapy and its limitations, describes the key pathogenic mechanisms in melanoma for which inhibitors have been tested, and summarizes the results of clinical trials involving molecularly targeted agents in this disease. WHAT THE READER WILL GAIN: There has been an explosion of preclinical and clinical research aimed at targeting the key molecular alterations in melanoma for therapeutic benefit. These findings will be presented and placed in the proper clinical context, affording information regarding the current molecular targets in the melanoma and the activity and limitations of therapeutic agents directed against them. TAKE HOME MESSAGE: Greater understanding of the pathogenic mechanisms underlying melanoma development has prompted the development of new therapeutic approaches aimed at counteracting these processes. While progress made over the past few years has generated considerable excitement, the benefits of these new therapies are still limited by incomplete and transient tumor regressions. It is hoped that with further investigation, particularly into mechanisms of treatment de novo and acquired treatment resistance, these limitations can be overcome.