Melanoma: from mutations to medicine

  1. David E. Fisher1,5
  1. 1Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
  2. 2The Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA;
  3. 3Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
  4. 4Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA

    Abstract

    Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field—breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many—sometimes-related, although also distinct—biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field.

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