Angler fish alone in the deep sea

The path to leptomeningeal metastasis

Jan Remsik & Adrienne Boire

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    • Adoptive cell therapies have emerged as promising approaches for the treatment of patients with cancer. Engineering cell therapies to confer resistance to small-molecule therapies, chemotherapies and antibody-based therapies will improve their utility and success. Here, Wellhausen, Baek and colleagues outline the key principles of engineering resistance and potential applications for haematopoietic stem cell transplantation and allogeneic immune cell therapies.

      • Nils Wellhausen
      • Joanne Baek
      • Carl H. June
      Review Article
    • Despite the success of immune-checkpoint inhibitors, many patients are at risk of developing immune-related adverse events. One of these is myocarditis or inflammation of the heart. Munir, Gutierrez and colleagues describe the data from preclinical models and patient samples, which have begun to provide a mechanistic understanding of myocarditis resulting from immune-checkpoint inhibitors, and present suggestions for improving both the diagnosis and treatment of patients experiencing this immune-related toxicity.

      • Amir Z. Munir
      • Alan Gutierrez
      • Javid J. Moslehi
      Review Article
    • In this Review, Polak, Zhang and Kuo discuss the currently available and rapidly evolving 3D tumour organoid models that capture the tumour immune microenvironment. They highlight opportunities for organoid-based investigations of tumour immunity, drug development and precision medicine.

      • Roel Polak
      • Elisa T. Zhang
      • Calvin J. Kuo
      Review Article
    • In this Review, Harris et al. summarize the dynamic changes of the immune breast tumour microenvironment (TME) that take place during disease progression and in response to treatment, and outline emerging therapies to target the immune TME in patients with breast cancer.

      • Michael A. Harris
      • Peter Savas
      • Sherene Loi
      Review Article
    • In this Roadmap, Boire et al. consider the immediate causes of mortality in patients with cancer, a topic not often considered in either preclinical or clinical research, and provide recommendations for how we can stimulate research to advance our mechanistic understanding of these causes with a long-term view to improving the quality of life for patients with late-stage cancer.

      • Adrienne Boire
      • Katy Burke
      • Erik Sahai
      Roadmap
  • Leighow et al. develop a strategy called the dual-switch selection gene drive platform, which enables the evolutionary dynamics of acquired resistance to be manipulated for therapeutic ends.

    • Anna Dart
    Research Highlight
  • Sex matters in metastasis, but it has received little attention in research. Here, we highlight the emerging and important roles of biological sex in metastasis and advocate for mechanistic and quantitative studies for the future development of sex-tailored therapies.

    • Yingsheng Zhang
    • Xue Li
    Comment
  • In this Journal Club, Maeng and Ku discuss a study demonstrating that profiling drug responses in patient-derived organoids can identify responders to various therapies.

    • Ju Eun Maeng
    • Ja-Lok Ku
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  • Lim et al. show that ASS1, silenced in many cancer types, is a metabolic checkpoint that, following DNA damage, halts cell cycle progression by restricting nucleotide synthesis and p53-related gene transcription.

    • Gabrielle Brewer
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  • In this study, Allan Balmain and colleagues used a mouse model to monitor stem cell networks at single-cell resolution during skin carcinogenesis, revealing two cancer stem cell states, rapid cycling and plasticity, between which cells can transition to drive tumour initiation, progression and therapy resistance.

    • Daniela Senft
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  • The practice of posting preprint manuscripts on servers such as bioRxiv has become increasingly common. In this Comment, Hindle and Sever explore the utility of preprints for advancing researchers careers.

    • Samantha Hindle
    • Richard Sever
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Six human body silhouettes, the three on the left are male-shaped, the three on the right female.

Sex differences in cancer

Sex differences begin at fertilization and affect nearly all body systems during development.
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