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Volume 20 Issue 4, April 2023

Protein degraders enter the clinic, inspired by the Review on p265.

Cover design: Simon Bradbrook

Comment

  • In 2022, the FDA approved numerous new drug and biologic agents, including targeted small molecules, immunotherapeutics, a gene therapy and a radiopharmaceutical. Several drug development challenges were also addressed, and key focus areas for the FDA Oncology Center of Excellence included ongoing monitoring of the Accelerated Approval programme and drug dose optimization.

    • Deepti Telaraja
    • Nicole Gormley
    • Richard Pazdur
    Comment

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Research Highlights

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Reviews

  • Data obtained using omics technologies can offer important insights into various aspects of chimeric antigen receptor (CAR) T cell therapy. In this Review, the authors provide an overview of the multidimensional profiling technologies that have been applied in investigations of CAR T cell therapy. They then discuss the ways in which multi-omics data obtained through such analyses can be used to elucidate CAR targets, factors associated with response or resistance to therapy, and mechanisms underlying the associated toxicities, which could potentially be exploited to improve the efficacy and safety of CAR T cell therapies.

    • Jingwen Yang
    • Yamei Chen
    • Leng Han
    Review Article
  • Lung cancers harbouring ‘rare’ alterations (defined as those with a prevalence of <5% of oncogene-driven lung cancers) can be detected in around a third of all oncogene-driven lung cancers and are diagnosed in thousands of patients each year. Advances in our understanding of tumour biology, diagnosis and the development of novel therapies are enabling increasing use of specific therapies targeting these alterations. In this Review, the authors provide an overview of the epidemiology, diagnosis, prognosis and treatment of patients with lung cancers harbouring these rare alterations. The importance of expedited drug approval pathways and cooperation between multiple stakeholders is also emphasized.

    • Guilherme Harada
    • Soo-Ryum Yang
    • Alexander Drilon
    Review Article
  • Cachexia is a multi-organ syndrome characterized by substantial weight loss that affects a majority of patients with cancer and contributes to cancer-related mortality. The authors of this Review discuss the contribution of both the tumour macroenvironment and microenvironment to the inflammatory and metabolic processes involved in cancer-associated cachexia and provide an overview of the therapeutic strategies developed to manage this syndrome.

    • Josep M. Argilés
    • Francisco J. López-Soriano
    • Silvia Busquets
    Review Article
  • Protein degraders constitute a new class of agents that eliminate, rather than just inhibit, their target proteins. These novel agents have recently entered testing in oncology trials, with initial data providing clinical proof of concept for the mechanism of action as well as the antitumour activity of heterobifunctional protein degraders. In this Review, the authors outline the progress in the development of such protein degraders for the treatment of cancer and consider prospects and potential challenges for these agents.

    • Deborah Chirnomas
    • Keith R. Hornberger
    • Craig M. Crews
    Review Article
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