Reviews & Analysis

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  • Transmissible cancer affects marine bivalve mollusks worldwide, but how genetic mechanisms influence cancer evolution and disease spread remains largely unexplored. Two new studies provide insights into the ancient origin of founder clones and the long-term tolerance of contagious cancer cells to extreme genome instability.

    • Anna Schönbichler
    • Andreas Bergthaler
    News & Views
  • Chimeric antigen receptor T cells and T cell-redirecting bispecific antibody therapies are changing the landscape of myeloma therapy. Two studies investigate the genetic and epigenetic resistance mechanisms that lead to relapse in patients receiving T cell-engaging therapies targeting B cell maturation antigen (BCMA) and GPRC5D.

    • Bruno Paiva
    • Jesús F. San-Miguel
    News & Views
  • Certain cancers disrupt metabolism, leading to the wasting syndrome known as cachexia. How tumor-induced mediators of cachexia induce changes in end organs is unclear. A study implicates the endothelium as an amplifier of tumor signals in fat, in which NOTCH1 promotes adipose tissue remodeling via retinoic acid, IL-33 and IGFBP3.

    • Brittany R. Counts
    • Teresa A. Zimmers
    News & Views
  • The nervous system regulates cancer progression, and the importance of neuron–glioma communication in tumor growth is evident in glioblastoma. This tumor-promoting communication presents a potential therapeutic axis, a concept reinforced by a study that identifies a specific potassium channel complex as a therapeutic target.

    • Stephen M. Robbins
    • Donna L. Senger
    News & Views
  • The development of immunotherapies for acute myeloid leukemia (AML) has been limited by a lack of known tumor-specific targets. A study now shows the feasibility of developing highly sensitive and selective T cell-receptor-based therapies against an HLA-A*02:01-associated peptide derived from a recurrent mutation in a subset of patients with AML.

    • Anca Apavaloaei
    • Claude Perreault
    News & Views
  • Jaffray and co-authors discuss progress in radiotherapy that has been driven by technological advances and ways to enable broad access to innovative radiation-based treatment modalities by aligning individualized therapy with global access needs.

    • David A. Jaffray
    • Felicia Knaul
    • Mary Gospodarowicz
    Review Article
  • Resected pancreatic cancer treated pre-operatively with chemotherapy is enriched for cells that co-express GATA6, KRT17 and CYP3A. Persistent expression of GATA6hi and KRT17hi is associated with poor survival after treatment with mFOLFIRINOX, but not gemcitabine. CYP3A-expressing drug detoxification pathways metabolize the prodrug irinotecan, a constituent of mFOLFIRINOX, leading to persistent drug tolerance.

    Research Briefing
  • Immunosuppressive myeloid cells, which are associated with resistance to anti-PD1 therapy in patients with glioblastoma, have high expression of KDM6B, an epigenetic enzyme. Deletion or inhibition of KDM6B reprograms the myeloid cells to an immunostimulatory phenotype and thereby overcomes resistance to anti-PD1 therapy in preclinical models of glioblastoma.

    Research Briefing
  • The recent design of mutation-selective KRAS inhibitors has led to US Food and Drug Administration approval of two inhibitors of KRAS(G12C), sotorasib and adagrasib. A study published in Nature reports the development of a first-in-class pan-KRAS-selective inhibitor. Here we comment on the current status of KRAS-targeting approaches.

    • Ryan B. Corcoran
    News & Views
  • The advantage of genomic monitoring over cytogenetics for clinical assessment of leukemia is illustrated by a case of pediatric acute lymphoblastic leukemia in which a lesion underlying lethal end-stage myeloid disease could be detected by whole-genome sequencing years before the risk manifested cytogenetically.

    • Lauren M. Harmon
    • Timothy J. Triche Jr
    News & Views
  • Treatment with immune checkpoint inhibitors (ICIs) has improved the survival of patients with metastatic melanoma. However, although ICIs are promising for achieving lasting clinical responses, only a subset of patients receive substantial benefit. Our results suggest that the IL-17 pathway supports the response of melanoma to dual ICI therapy and might represent a biomarker for patient stratification.

    Research Briefing
  • This study reveals the previously underappreciated roles of CD25 (IL-2 receptor subunit-α) in IL-2 biology and cancer immunotherapy and provides mechanistic insights into the rational design of more-effective IL-2-based therapeutic agents for cancer treatment.

    Research Briefing
  • CD8+ T cells recognize tumor-associated antigens presented by major histocompatibility complex (MHC) class I molecules. How CD8+ T cells eliminate cancer cells deficient in MHC class I has been unclear. A study now shows that adaptive CD8+ T cell activation induces expression of the innate receptor NKG2D for the elimination of MHC class I–deficient tumors.

    • Christopher E. Rudd
    News & Views
  • Glioblastoma is an aggressive brain tumor with a highly immunosuppressive environment that responds poorly to immune checkpoint inhibitors. A study shows that SIGLEC9+ monocyte-derived macrophages are enriched in glioblastomas that do not respond to immune checkpoint inhibitors, and targeting this receptor synergizes with immunotherapy.

    • Thomas U. Marron
    • Jennifer L. Guerriero
    News & Views
  • Pathological diagnosis relies on morphological assessment of tissue using histological staining and molecular phenotyping through immunostaining that must be performed on separate tissue sections. Orion is a newly reported methodology that facilitates multiplexed immunostaining with histological staining on the same slide.

    • Ashley N. Anderson
    • Summer L. Gibbs
    News & Views