title: Drug targeting of oncogenic pathways in melanoma.
abstract: Melanoma continues to be one of the most aggressive and morbid malignancies once metastatic. Overall survival for advanced unresectable melanoma has not changed over the past several decades. However, the presence of some long-term survivors of metastatic melanoma highlights the heterogeneity of this disease and the potential for improved outcomes. Current research is uncovering the molecular and genetic scaffolding of normal and aberrant cell function. The known oncogenic pathways in melanoma and the attempts to develop therapy for them are discussed. The targeting of certain cellular processes, downstream of the common genetic alterations, for which the issues of target and drug validation are somewhat distinct, are also highlighted.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, 3400 Spruce Street, 16 Penn Tower, Philadelphia, PA 19104, USA. leslie.fecher@uphs.upenn.edu
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Fecher
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Amaravadi
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schuchter
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D016503:Drug Delivery Systems; D005544:Forecasting; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases