title: Playing Polo-Like Kinase in NRAS-Mutant Melanoma.
abstract: NRAS-mutant melanomas are extremely aggressive and highly resistant to currently available therapeutic modalities. Hence, new targets and therapeutic strategies for NRAS-driven melanomas are needed. As blocking NRAS directly has not been possible thus far, targeting downstream NRAS effectors, such as MAPK/ERK kinase (MEK), is being evaluated as an alternative therapeutic approach. However, blocking this pathway alone has limited efficacy. In this issue, Posch et al. report on a combination approach co-targeting polo-like kinase 1 and MEK in NRAS-mutant melanomas. This combination triggers a dual blockade of the cell cycle machinery, leading to apoptosis, and providing a new strategy to treat NRAS-mutant melanoma.
authors.affiliation: The Wistar Institute, Molecular and Cellular Oncogenesis Program & Melanoma Research Center, Philadelphia, Pennsylvania, USA.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chen
authors.affiliation: The Wistar Institute, Molecular and Cellular Oncogenesis Program & Melanoma Research Center, Philadelphia, Pennsylvania, USA. Electronic address: jvillanueva@wistar.org.
authors.forename: Jessie
authors.initials: J
authors.lastname: Villanueva
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1