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Coppé and colleagues define a resistance mechanism to combination BRAF- and EGFR-targeted therapy in BRAFV600E colorectal cancers that could be overcome in vitro and in vivo by repurposing COX2 inhibitors.
Fendt and colleagues find that pre-metastatic niche formation and a high-fat diet increase palmitate availability in future organs of metastases and show that breast cancer cells use palmitate to generate acetyl-CoA, acetylate the NF-κB subunit p65 and induce pro-metastatic signaling.
Iavarone and colleagues develop a computational approach called SPINKS to identify master kinases for functional subtypes of human glioblastoma defined using integrated multi-omics data, which show potential as subtype-specific therapeutic targets.
Jäger and colleagues analyze single-base substitution and indel mutational signatures across 27 pediatric cancer types, revealing marked differences in mutational patterns compared with adult cancers and insights into underlying molecular mechanisms.
Lau and colleagues show that the dietary addition of the sugar l-fucose enhances immunotherapy response in melanoma models. This is mediated via the fucosylation and cell surface enrichment of HLA-DRB1 and induction of anti-tumor immunity.
Qiu et al. show that chronic interferon (IFN) stimulation establishes an epigenetic signature of inflammatory memory in tumor cells, resulting in elevated levels of IFN-stimulated genes that sustain immune cell dysfunction when IFN is low.
Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.
Gulhati et al. demonstrate therapeutic efficacy for combinatorial administration of 41BB agonist, LAG3 antagonist and a CXCR1/2 inhibitor in murine pancreatic cancer models, resulting in a remodeled tumor microenvironment.
Silva and colleagues develop a network-based HDAC6 score which could predict sensitivity to the HDAC6 inhibitor ricolinstat in preclinical models, as well as patients with HR+/HER2− breast cancer that received ricolinstat in a phase 1b clinical trial.
Lasry and Nadorp et al. use single-cell RNA sequencing and CITE sequencing to reveal inflammatory gene expression in a subset of pediatric and adult patients with acute myeloid leukemia that associates with changes in the immune microenvironment and generate an inflammatory score with prognostic potential.
Oh and colleagues demonstrate that the DUSP6–RSK1 axis is involved in the transformation of myeloproliferative neoplasms to secondary acute myeloid leukemia and that DUSP6 mediates the response to JAK2 inhibition.
Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.
Keppler and colleagues show that individuals with hematological cancers rapidly develop potent infection-neutralizing antibodies and a robust T cell response against several SARS-CoV-2 variants of concern in response to mRNA vaccination.
Mazzone and colleagues identify the bicarbonate transporter SLC4A4 as highly abundant in epithelial duct cells in pancreatic cancer and show that its inhibition mitigates acidosis in the tumor, thereby alleviating immune suppression and overcoming immunotherapy resistance.
Earnest-Noble et al. report the opposing regulation during breast cancer metastasis of two isoleucyl tRNAs that decode synonymous codons, leading to divergent regulation of metastatic growth by influencing translation of growth-regulating genes.
Shahbandi et al. find that cancer cells that survive chemotherapy (CT) activate two immune-modulatory programs characterized by IFN response genes and CD274 or p53 signaling and CD80 expression. Targeting these pathways enhances the CT response.
Spurr et al. identify high pretreatment aneuploidy score as a potential biomarker in patients with NSCLC who benefit from concurrent radiation and immune checkpoint inhibition, in immunogenomic analysis of data from a phase I clinical trial.
Karam and colleagues report a phase I/Ib trial in patients with HNSCC treated with neoadjuvant SBRT and anti-PD-L1, and perform high-dimensional analyses of immune correlates of response in the tissue microenvironment and peripheral blood.
Bernards and colleagues identify cFLIP as a common dependency of cancer cells by conferring protection from senolytic-induced cell death. They nominate combination of DR5 activation and cFLIP suppression for enhanced killing of senescent cancer cells.
Nishiga and colleagues show therapeutic efficacy for a combination of radiotherapy and CD47 blockade, which also elicits an abscopal effect mediated by macrophages migrating into non-irradiated tumor sites and phagocytosing cancer cells.