Reviews & Analysis

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  • Increasing evidence links RNA methyltransferases to DNA damage repair. METTL16 is now shown to antagonize homologous recombination by preventing DNA-end resection via MRE11. Thus, METTL16 may represent a cancer vulnerability that can be used to identify patients able to benefit from combination therapies with DNA-damaging agents.

    • Marcelo Perez-Pepe
    • Claudio R. Alarcón
    News & Views
  • Therapeutic resistance in prostate cancer can be driven by lineage plasticity, but the mechanisms behind this are unclear, and therapies to prevent or reverse the process are nonexistent. A new study reveals the JAK/STAT signaling axis as a driver of lineage plasticity with tremendous therapeutic potential.

    • Nicholas J. Brady
    • Christopher E. Barbieri
    News & Views
  • The identification of tumor-reactive T cells using phenotypic markers is now well established in treatment-naive tumors. It is unclear, however, whether these markers can also be useful after immune checkpoint blockade (ICB). A new study finds that CXCL13 expression robustly identifies tumor-reactive T cells before and after ICB and is associated with treatment response.

    • Paulien Kaptein
    • Daniela S. Thommen
    News & Views
  • Mesenchymal-like and pluripotency-like programs coordinate the dissemination and long-lived dormancy of early breast cancer cells. The transcription factor ZFP281 controls these programs, preventing the acquisition of an epithelial-like proliferative phenotype and serving as a previously unrecognized barrier to metastasis.

    Research Briefing
  • Immunotherapy has shown great promise in the treatment of patients with advanced non-small-cell lung cancer. We show that integration of data collected during diagnostic clinical work-up with machine learning has the potential to improve predictions of response to immunotherapy and to identify the patients most likely to benefit.

    Research Briefing
  • Immune checkpoint inhibitors (ICIs) are effective for many cancers but can be limited by inflammatory toxicities. Little is known about how ICIs affect the reproductive system. New research in animal models with and without tumours demonstrates that ovarian reserves are depleted in mice treated with ICIs, which may influence fertility.

    • Stephanie A. Roberts
    • Michael Dougan
    News & Views
  • Structural variants (SVs), such as copy-number alterations, rearrangements and aneuploidies, are common somatic changes in cancer genomes and rich sources of driver oncogenes, but reconstructing these from sequencing data is a challenge. Two new studies shed light on the diversity and importance of the SV landscape in cancer.

    • Paul S. Mischel
    • Vineet Bafna
    News & Views
  • Brody and colleagues discuss the current status and potential of cancer vaccines, highlighting challenges and opportunities to advance promising candidates to the clinic.

    • Matthew J. Lin
    • Judit Svensson-Arvelund
    • Joshua D. Brody
    Review Article
  • How pancreatic ductal adenocarcinoma persists despite limited nutrients within the tumor microenvironment warrants further investigation. A study now identifies a metabolic mechanism wherein NUFIP1 induces release of nucleosides from cancer-associated fibroblasts, leading to activation of MYC-dependent glucose consumption and tumor growth.

    • Holly Sandborg
    • Mara H. Sherman
    News & Views
  • Though HER2 (ERBB2) exon 20 insertion mutations occur in ~2% of non-small-cell lung cancers, molecular targeted therapies for such cancers have been lacking. A study now identifies selective HER2 inhibitors that have marked efficacy against tumors driven by HER2 exon 20 insertions, without inhibiting wild-type EGFR activity.

    • Ryohei Katayama
    News & Views
  • Despite the remarkable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of hematological malignancies, this strategy remains challenging in solid tumors. One major obstacle is the hostile immunosuppressive tumor microenvironment. New research demonstrates that targeting PARP11 can overcome this immunosuppression and boost CAR T cell efficacy through stabilization of IFNAR1.

    • Isabelle Munoz
    • Paul A. Beavis
    News & Views
  • Inhibition of XPO1-mediated nuclear export by selinexor represents a promising therapeutic strategy in acute myeloid leukemia. Because XPO1 is not specific for tumor-suppressive proteins, selinexor may also activate pro-oncogenic processes. A study now shows that inhibition of selinexor-induced, purinergic receptor–mediated AKT activation potentiates its anti-leukemic activity.

    • Stefanie Göllner
    • Carsten Müller-Tidow
    News & Views
  • Lavie et al. review the recent advances in the field of cancer-associated fibroblasts, including their tissue-specific complexity and overall plasticity, as revealed by single-cell technologies.

    • Dor Lavie
    • Aviad Ben-Shmuel
    • Ruth Scherz-Shouval
    Review Article
  • Many patients with colorectal cancer (CRC) relapse after chemotherapy. Tumor cells that do not completely adapt to their environment (owing to an incomplete set of CRC driver mutations) enter a latent state, in which the expression of Mex3a is upregulated. Mex3a+ cells are chemoresistant and reactivate after treatment, which leads to regeneration of the disease.

    Research Briefing
  • The phenotypes of γδ T cells infiltrating human tumors and their role in anti-tumor immunity remain poorly understood. A new study demonstrates that Vδ1 lymphocytes with cytolytic potential and features of tissue-resident-memory differentiation are predictive of survival in patients with non–small-cell lung cancer.

    • Jose R. Conejo-Garcia
    • Patrick Innamarato
    News & Views
  • Prognostic information for patients with ovarian cancer is captured in clinico-genomic data, histopathology slides and computed tomography imaging; however, how to integrate these data is unclear. A study now presents a method for combining complementary data types to stratify risk and aid treatment selection in patients with ovarian cancer.

    • Hanna M. Hieromnimon
    • Alexander T. Pearson
    News & Views
  • Tumor mutational burden (TMB) has received significant attention within ongoing pursuits of biomarkers of response to immune checkpoint inhibitors, and notably received FDA approval as a companion diagnostic biomarker for pembrolizumab. Here, four experts discuss the utility, challenges, and open questions surrounding TMB in the context of cancer immunotherapy.

    • Valsamo Anagnostou
    • Alberto Bardelli
    • Samra Turajlic
  • Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).

    • Liu He
    • Arvin C. Dar
    News & Views