ABSTRACT
Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.
Subject(s)
Melanoma/drug therapy , Molecular Targeted Therapy , Skin Neoplasms/drug therapy , Extracellular Signal-Regulated MAP Kinases/physiology , Humans , Indoles/therapeutic use , MAP Kinase Kinase Kinases/physiology , Melanoma/genetics , Melanoma/metabolism , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/physiology , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Sulfonamides/therapeutic use , VemurafenibABSTRACT
BACKGROUND: Rapid immunostaining in Mohs micrographic surgery (MMS) has been extensively reviewed in the recent literature. Despite the recent attention, there is relatively little information on how frequently these techniques are actually utilized and the current attitudes of the Mohs community towards immunohistochemical (IHC) stains. OBJECTIVE: We attempted to obtain information on the utilization and attitudes towards the use of rapid immunostaining in Mohs through a survey of fellowship-trained Mohs surgeons. MATERIALS AND METHODS: A twenty-five question survey was sent to members of the American College of Mohs Surgery (ACMS) through various methods including SurveyMonkey(®) , email, fax, and Metrofax(®) . RESULTS: A total of 378 surveys were completed. These responses represent a cross-section of fellowship-trained members of the ACMS. CONCLUSIONS: The vast majority of respondents felt as though IHC stains could be used reliably in Mohs. A subset of responses indicated that the most common reasons for not using IHC stains are time consumption, lack of education, and startup and/or maintenance costs. An increase in immunostain usage over 10 years ago appears to correlate with the activity in the literature. There may be an underutilization of IHC staining in fellowship programs, as indicated by respondents' opinions.