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Showing 1–11 of 11 results
Advanced filters: Author: Shiva Malek Clear advanced filters

  • Therapies targeting RAS, a small GTPase that is frequently altered in cancer, are explored in this poster.

    • Amanda R. Moore
    • Scott C. Rosenberg
    • Shiva Malek
    Multimedia
    Nature Reviews Drug Discovery
    P: 1

  • The mechanism of action of three different allosteric MEK inhibitors that target the MAP kinase pathway is investigated, and their efficacy is shown to be explained by the distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours; this work provides a rationale for designing more effective cancer therapies for these common genetic subtypes of cancer.

    • Georgia Hatzivassiliou
    • Jacob R. Haling
    • Marcia Belvin
    Research
    Nature
    Volume: 501, P: 232-236

  • The application of a potent lactate dehydrogenase (LDHA) inhibitor GNE-140 on pancreatic cancer cells revealed that resistance to GNE-140 is attributable to an AMPK–mTOR–S6K-mediated switch in utilization from glycolysis to oxidative phosphorylation.

    • Aaron Boudreau
    • Hans E Purkey
    • Thomas O'Brien
    Research
    Nature Chemical Biology
    Volume: 12, P: 779-786

  • The RAS–RAF signalling pathway is an attractive target for drug development in oncology, and several RAF inhibitors are being tested in clinical trials. Here and in an accompanying paper, RAF inhibitors are shown to have opposing roles, functioning as either inhibitors or activators of RAF depending on the cellular context and mutational status of RAF. The mechanistic basis for these opposing roles is dissected. The results have implications for the clinical use of these inhibitors and for the design of kinase inhibitors.

    • Georgia Hatzivassiliou
    • Kyung Song
    • Shiva Malek
    Research
    Nature
    Volume: 464, P: 431-435

  • RAS proteins, which are frequently altered in cancer, were once considered undruggable, but compounds targeting some mutant RAS proteins have recently demonstrated clinical efficacy. In this Review, Malek and colleagues explore how these and other drugs that target RAS or associated pathways might be used effectively, particularly in combinations, and discuss other RAS-targeted therapies in the pipeline.

    • Amanda R. Moore
    • Scott C. Rosenberg
    • Shiva Malek
    Reviews
    Nature Reviews Drug Discovery
    Volume: 19, P: 533-552