Research Highlights

Kalkavan et al. find sublethal cytochrome c release leads to a caspase-independent, ATF4-dependent drug-tolerant persister phenotype.

Using single-cell RNA-seq and functional analysis in prostate cancer organoids and mouse models, Chan et al. identify inflammatory JAK–STAT signalling to drive the transition of adenocarcinomas to neuroendocrine prostate cancer.

Ma et al. demonstrate that platelets suppress liver tumour growth in the context of non-alcoholic fatty liver disease through T cell-dependent antitumour immunity.

Xu, Yan et al. show that the hypothalamic–pituitary unit produces α-melanocyte-stimulating hormone in tumour-bearing mice, to promote myelopoiesis and immunosuppression.

Using a reporter system in a mouse model of pancreatic cancer, Baslan et al. detail the progression of genomic disruption following p53 loss.

In two studies published concurrently, Pal et al. and Shi et al. reveal that certain gliomas rely on the de novo synthesis of pyrimidines. These studies go on to demonstrate the effectiveness of brain-penetrant inhibitors of de novo pyrimidine synthesis in preclinical models of glioma.

Chen et al. have developed a preclinical platform that enables the reprogramming of locoregional macrophages and microglia in situ with CD133-directed chimeric antigen receptors, which leads to the phagocytosis and removal of residual glioma stem cells after tumour debulking.

Barkley and colleagues conducted single-cell RNA sequencing of almost 20,000 malignant cells and identified cancer cell states that are both common and different across tumour types, and revealed how these states interact with the tumour microenvironment.

Seki et al. show that exposure to cold suppresses tumour growth in mice through increasing glucose uptake and thermogenesis in brown adipose tissue.

Venkataramani et al. used longitudinal intravital two-photon imaging to track migrating glioblastoma cells in vivo, and identified a seemingly unconnected cell subpopulation that was responsible for colonization of the brain by mimicking neuronal mechanisms of movement.

Using single-cell transcriptomic data, Joanito et al. reveal that colorectal cancers can be defined by the presence of one of two major intrinsic epithelial subtypes, and present a refined molecular classification system for these cancers.

Finding sex differences in the response of patients with melanoma to BRAF/MEK-targeted therapy, Vellano et al. show that this effect is mediated by androgen receptor expression and demonstrate that androgen receptor blockers can enhance treatment response.

Diamantopoulou et al. have found that in both mouse models and patients with breast cancer, the timing of spontaneous circulating tumour cell production coincides with sleep.

Zhang et al. demonstrate that the adenosine deaminase ADAR1 prevents responsiveness to immune checkpoint blockade (ICB) through acting on cellular Z-nucleic acids, and show inducing Z-nucleic acid formation can induce tumour sensitivity to ICB.

Chen et al. show that gliomagenesis in the olfactory bulb of the brain is directly related to olfactory perception in mice.

Reticker-Flynn et al. show that exposure of melanoma cells to interferons and immune cells within lymph nodes leads to immune tolerance that promotes metastasis of both these cells and primary tumour cells.

Crist et al. set out to investigate what makes the colonization of skeletal muscle by disseminated tumour cells (DTCs) so rare and found that this niche enforces persistent oxidative stress on DTCs that cannot be overcome and therefore, restrains their proliferation.

Lv, Liu, Mo and colleagues demonstrate that in pancreatic ductal adenocarcinoma cells, gasdermin E transports the transcription factor YBX1 to the nucleus, where it promotes the expression of mucins, thereby providing tumour cells with a barrier against digestive enzymes.

Guan, Polesso, Wang, et al. report that androgen receptor blockade, in addition to androgen deprivation therapy, enhances the response of T cells to anti-PD1 immune checkpoint inhibitors.