Volume 19 Issue 5, May 2019

In a study published in Nature Biotechnology, Aalipour et al. have engineered macrophages to create biocompatible diagnostic sensors that can detect tumours as small as 25–50 mm³ in mice, even with co-occurring inflammation.

Elia et al. show that breast cancer cells in the lung metastatic niche are dependent on pyruvate uptake to promote extracellular matrix remodelling and metastatic growth, which can be targeted therapeutically.

Two studies show that in the presence of KRAS pathway inhibition, KRAS-mutant pancreatic ductal adenocarcinomas become dependent on autophagy for survival. Removing this protective mechanism through combining MEK or ERK inhibitors with inhibitors of autophagy is likely to be therapeutically beneficial.

In a study published in Nature, Obradović et al. have identified that breast cancer progression in mice is associated with increased levels of stress hormones resulting in activation of the glucocorticoid receptor at secondary sites, enhanced colonization and decreased survival.

Hu et al. demonstrate that in pancreatic cells, genomic instability and mutations in KRAS, which drive carcinogenesis, can be promoted by high glucose-induced deregulation of deoxyribonucleotide synthesis.

Parada and colleagues have identified a novel small-molecule inhibitor of oxidative phosphorylation, which exerts cancer-cell-specific toxicity and inhibits glioblastoma growth in mouse models.

Failure of anticancer immune responses is often due to T cell dysfunction, but the molecular mechanisms underlying this are incompletely understood. Two papers in Nature now identify NR4A transcription factors as key drivers of T cell dysfunction.

Omomyc, a MYC dominant-negative gene product that is used to inhibit MYC for research purposes, can penetrate cancer cells in vitro and in vivo, bringing it closer to evaluation in the clinic.

Recurrent oncogenic chromosomal rearrangements frequently involve genes required for chromatin regulation and transcriptional control. This Review discusses mechanistic insights into the chromatin-based functions of many of these oncogenic fusion proteins that are guiding the design of new therapeutic approaches.

This Opinion discusses three different mechanisms by which high-dose vitamin C can be selectively toxic to cancer cells. These findings from preclinical studies will be beneficial for the design of clinical trials testing high-dose vitamin C as an anticancer therapy.

The existence of extrachromosomal DNA (ecDNA) in cancer was first described decades ago, but recent reports of oncogene amplification on ecDNA have reinvigorated interest in this field. This Perspectives article discusses the potential implications of oncogene amplification on ecDNA in cancer.

This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.