Research Highlights in 2021

Nie et al. performed metabolomics profiling on samples obtained from patients during the development of invasive lung adenocarcinoma and showed that metabolic pathways are progressively disrupted.

Hung, Yost, Xie et al. show that extrachromosomal DNAs (ecDNAs) are held together in hubs in the nucleus and that intermolecular interactions between ecDNAs can enhance oncogene expression.

Li, Xiao and colleagues show that antihistamines might increase the efficacy of immune checkpoint blockade.

Liu et al. show that glycogen accumulates in pre-malignant liver cells by undergoing liquid–liquid phase separation and, by sequestering Hippo kinases MST1 and MST2, promotes YAP-driven tumorigenesis.

Klemm et al. examined the role of tumour-associated macrophages (TAMs) at different stages of brain metastasis in mouse models and found that targeting TAMs by inhibiting both CSF1R and STAT5 might have long-lasting efficacy and prevent resistance.

Pernigoni et al. present a unique mode of non-genetic resistance accounting for castration-resistant prostate cancer that is mediated by androgen-synthesizing gut microbiota.

Neuhöfer et al. have identified a rare subpopulation of pancreatic acinar cells in the exocrine compartment that renews the pancreas by fuelling clonal expansion. When harbouring Kras mutations, these acinar cells accelerated clone formation and might represent an early cancer precursor lesion.

Canale et al. engineered the bacterial strain Escherichia coli Nissle 1917 to recycle ammonia into arginine, and showed synergistic responses with anti-programmed cell death 1 ligand 1 therapy in tumour-bearing mice when injected intratumourally or given systemically.

Two recent studies have found that both the adaptive immune system and inflammation can drive the selection of cells carrying mutations that facilitate tumour initiation.

Using zebrafish and human pluripotent stem cell-derived models of melanoma, Baggiolini, Callahan et al. demonstrate that cells expressing progenitor-like programmes and specific chromatin-modifying enzymes are more readily transformed by BRAF^V600E.

Oren et al. developed a lentiviral barcode library, called Watermelon, to characterize the rare population of cycling persister cancer cells that arise during the course of drug treatment and promote tumour relapse.

Shiao et al. demonstrate that commensal bacteria and fungi have opposing roles to play in the responses of tumours to radiotherapy.

Haas et al. show that acquired resistance to a targeted therapy can result in cross-resistance to immunotherapy through the induction of an immune-evasive microenvironment.

Two studies published in Nature Cancer and Nature Communications describe the discovery of first-in-class, potent and specific inhibitors of Polϴ to target homologous recombination-deficient cancers.

Casanova-Acebes et al. show that tissue-resident macrophages provide a unique niche for tumour cells in the lung to promote invasiveness and regulatory T cell-mediated immune suppression.

Three studies published in Nature examine how competition influences tumour initiation in the intestinal epithelium.

Torrino et al. report that extracellular matrix stiffening stabilizes microtubules by glutaminolysis-dependent microtubule glutamylation, thereby promoting breast cancer progression.

McDowell et al. present mechanistic insights on how obesity-associated neutrophils can modify the lung microenvironment to promote breast cancer cell extravasation.

Zhang et al. show that, in mouse models, bone metastases can seed metastases in other organs and that this is driven by EZH2-mediated epigenetic reprogramming to promote stem cell-like features.

Kaczanowska, Beury et al. find that the presence of a distant tumour induces immunosuppressive programmes in the lung, and that treatment of mice with genetically engineered myeloid cells expressing interleukin-12 reduces metastatic burden and improves survival.