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Na et al. identify KMT2C deficiency as a driver of small cell lung cancer metastasis and demonstrate that it leads to epigenetic reprogramming through histone and DNA hypomethylation by upregulating DNMT3A.
Golub and colleagues identify the phosphate exporter XPR1 as a therapeutic vulnerability in ovarian and uterine cancers, and show that phosphate efflux inhibition reduces tumor cell viability through accumulation of intracellular phosphate.
Jänne and colleagues discover and characterize an allosteric EGFR inhibitor with efficacy against therapy-resistant mutations and show preclinical efficacy as monotherapy and in combination in patient-derived xenograft models.
Agnihotri and colleagues show that loss of the MAT2A enzyme of the methionine cycle induces a global depletion of H3K36me3 and extends survival in glioma models, representing a potential therapeutic vulnerability.
Li and colleagues use single-cell techniques to identify features of T cells in the tumor and draining lymph nodes involved in the efficacy of immune checkpoint blockade combined with a neoantigen vaccine in preclinical models.
Pramesh and colleagues report a study on the risk factors and outcomes in a large cohort of patients with cancer infected with SARS-CoV-2 from a tertiary care cancer center in India.
Lim and colleagues present the UK PROSECO study where they assess humoral and cellular immune responses to one, two and three doses of vaccination against SARS-CoV-2 in patients with B-cell malignancies in a prospective observational study.
Hua and colleagues develop CAR T cells targeting CDH17 and show that they are effective at suppressing tumor growth in mouse and human models of neuroendocrine and gastrointestinal solid tumors, without damaging healthy tissues in preclinical models.
Celià-Terrassa and colleagues identify LCOR-low cancer stem cells driving tumor immunity and propose LCOR induction with mRNA therapy as an enhancer of immunotherapy response.
Alvarez and colleagues develop a bispecific anti-PD-1–GITR-L agonist that activates T cells via a mechanism distinct from those found with individual PD-1 and GITR-L agonists and demonstrate its antitumor activity in mice and nonhuman primates.
Amit and colleagues report that the specific interaction of a CD4+PD-1+CXCL13+ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.
Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
Tamborero and colleagues develop the Molecular Tumor Board Portal, a virtual platform that integrates and interprets genomics and clinical data from prospective clinical studies, to support clinical decision-making for precision oncology.
Welm and colleagues present a biobank of human-derived xenografts and organoids and demonstrate its value for high-throughput drug screening and applied precision medicine.
Malanchi and colleagues demonstrate that irradiation in healthy lung tissue leads to an alveolar repair response orchestrated by neutrophils and Notch signaling that promotes metastatic colonization of disseminated tumor cells in the lung.
Gavert et al. develop an organotypic platform to define individual-specific therapies, show that it can reflect in vivo PDX responses and find that combined MEK and Src inhibition is effective in a large panel of human colorectal tumors.
Xie et al. show that loss of SETD2-mediated H3K36me3 promotes kidney cancer metastasis through epigenetic remodeling and uncover actionable therapeutic vulnerabilities in these tumors.
Saur and colleagues perform a high-throughput combinatorial drug screen and identify a synergistic combination between nintedanib and trametinib that sensitizes mesenchymal PDAC to immune checkpoint blockade.
Sun and colleagues identify lnc-CTHCC, a cancer-testis lncRNA that binds to hnRNP K, activates YAP1 transcription and promotes hepatocellular carcinogenesis.