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Volume 19 Issue 8, August 2020

Cracking RAS as an anticancer target, inspired by the Review on p533.

Cover design: Susanne Harris, target image from EgudinKa/iStock/Getty Images Plus.


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News & Analysis

  • Despite recent setbacks with p53-activating small molecules including the nutlins, the cancer target keeps drug hunters coming back for more. Could immuno-oncology combinations, stapled peptides and targeted degraders unleash the therapeutic potential of the ‘guardian of the genome’?

    • Asher Mullard
  • News in Brief

  • Biobusiness Briefs

  • An Audience With

    • Leena Gandhi, a thoracic oncologist, started working with cancer immunotherapies in 2008 in one of the first trials of the PD1 inhibitor nivolumab and has been hooked on the field ever since. In the subsequent decade, she coordinated dozens of immuno-oncology trials — first at Dana Farber Cancer Institute, then at New York University’s Perlmutter Cancer Center — including a seminal study defining the use of PDL1 as a biomarker for PD1 inhibition in lung cancer. After a 2-year stint overseeing immuno-oncology at Eli Lilly, Gandhi is now returning to the Dana Farber Cancer Institute as Director of its new Center for Therapeutic Innovation. She spoke with Asher Mullard about the appeal of immunotherapies, how they have impacted academic drug development, and the hunt for better biomarkers that can unravel their complicated biological effects.

      • Asher Mullard
      An Audience With
  • From the Analyst's Couch

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Research Highlights

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  • Several biological phenomena alter the ageing process. This Review discusses the most promising agents to slow ageing, separating them into two tiers based on their efficacy and evidence. The potential use of some interventions in clinical trials to expand overall healthspan as well as how those interventions could be assessed are also discussed.

    • Linda Partridge
    • Matias Fuentealba
    • Brian K. Kennedy
    Review Article
  • 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


    Review Article
  • Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) — a key mediator of cell death and inflammation — is activated in human diseases. Here, Yuan and colleagues discuss current understanding of RIPK1 biology and its association with diseases including inflammatory and autoimmune disorders, neurodegenerative diseases and sepsis. The clinical development of small-molecule RIPK1 inhibitors and associated challenges are discussed.

    • Lauren Mifflin
    • Dimitry Ofengeim
    • Junying Yuan
    Review Article
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