Nature Reviews Cancer, Published online: 17 May 2019; doi:10.1038/s41568-019-0149-1This Opinion article provides an overview of the mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour progression.
Nature Reviews Cancer, Published online: 15 May 2019; doi:10.1038/s41568-019-0144-6Tertiary lymphoid structures (TLSs) form outside of lymphoid tissues at sites of chronic inflammation, including tumours. This Review describes the evidence demonstrating that TLSs are critical for generating antitumour immune responses and are associated with better prognosis in certain cancer types. It also presents potential strategies aimed at inducing TLS neogenesis to improve clinical responses in poorly immunogenic cancers.
Going to extremes: determinants of extraordinary response and survival in patients with cancer
Going to extremes: determinants of extraordinary response and survival in patients with cancer, Published online: 10 May 2019; doi:10.1038/s41568-019-0145-5For any given cancer type, there are patients who have exceptionally favourable or atypically poor responses to treatment and overall survival. This Opinion article outlines approaches to identify and study these patients at the extremes of the spectrum with a view to gain insights that will be applicable to the wider patient population.
Prophylactic TNF blockade reduces autoimmune toxicity
Prophylactic TNF blockade reduces autoimmune toxicity, Published online: 09 May 2019; doi:10.1038/s41568-019-0152-6In a study published in Nature, Perez-Ruiz et al. report that prophylactic tumour necrosis factor (TNF) blockade reduces gastrointestinal immune-related adverse events in mice treated with dual immune-checkpoint inhibition, providing a clear preclinical rationale for the clinical investigation of such strategies.
E-selectin fills two needs for metastasis
E-selectin fills two needs for metastasis, Published online: 07 May 2019; doi:10.1038/s41568-019-0151-7Esposito et al. describe a mechanism for the simultaneous induction of mesenchymal-to-epithelial transition and stem cell traits in disseminating breast cancer cells in the bone, and provide therapeutic opportunities to prevent initiation of bone metastasis.
The broken cycle: E2F dysfunction in cancer
The broken cycle: E2F dysfunction in cancer, Published online: 03 May 2019; doi:10.1038/s41568-019-0143-7Alterations of the cyclin-dependent kinase (CDK)–RB–E2F axis occur in virtually all cancers and result in heightened oncogenic E2F activity and uncontrolled proliferation. This Review discusses the activities of E2F proteins in cancer and therapeutic strategies to target this oncogenic pathway.
Better safe than sorry: a potential prophylactic treatment for brain metastasis
Better safe than sorry: a potential prophylactic treatment for brain metastasis, Published online: 03 May 2019; doi:10.1038/s41568-019-0150-8Benbenishty et al. find that prophylactic administration of CpG-C, a Toll-like receptor 9 agonist, significantly reduces the development of brain metastasis in preclinical mouse models via the activation of microglial cells that kill and phagocytose the tumour cells.
Macrophage manipulation, Published online: 02 May 2019; doi:10.1038/s41568-019-0148-2Macrophage manipulation
Prioritizing synthetic lethal targets with functional genomics
Prioritizing synthetic lethal targets with functional genomics, Published online: 29 April 2019; doi:10.1038/s41568-019-0147-3Four papers report that cancer cells with microsatellite instability, which arises owing to defects in DNA mismatch repair, are selectively vulnerable to knockout of WRN, a RecQ family DNA helicase that could potentially be targeted with small molecules.
Platelets with dangerous cargo
Platelets with dangerous cargo, Published online: 29 April 2019; doi:10.1038/s41568-019-0146-4In a study published in Nature Medicine, Malehmir et al. have identified how platelet recruitment contributes to the development of nonalcoholic steatohepatitis and hepatocellular carcinoma in response to high-fat diets in mice.
Cancer overdiagnosis: a biological challenge and clinical dilemma
Cancer overdiagnosis: a biological challenge and clinical dilemma, Published online: 25 April 2019; doi:10.1038/s41568-019-0142-8The implementation of screening tests for certain cancers has led to the phenomenon of overdiagnosis, whereby a cancer is diagnosed that would otherwise not go on to cause symptoms or death. This Opinion article discusses the effects of overdiagnosis and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour biology and the tumour microenvironment.
Targeting cancer vulnerabilities with high-dose vitamin C
Targeting cancer vulnerabilities with high-dose vitamin C, Published online: 09 April 2019; doi:10.1038/s41568-019-0135-7This 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.
Long path to MYC inhibition approaches clinical trials
Long path to MYC inhibition approaches clinical trials, Published online: 09 April 2019; doi:10.1038/s41568-019-0141-9Omomyc, 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.
Targeting chromatin complexes in fusion protein-driven malignancies
Targeting chromatin complexes in fusion protein-driven malignancies, Published online: 08 April 2019; doi:10.1038/s41568-019-0132-xRecurrent 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.
Searching for a diagnosis
Searching for a diagnosis, Published online: 05 April 2019; doi:10.1038/s41568-019-0140-xIn 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.
Targeting cancer cell metabolism in glioblastoma
Targeting cancer cell metabolism in glioblastoma, Published online: 03 April 2019; doi:10.1038/s41568-019-0139-3Parada 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.
Eliminating protective autophagy in KRAS-mutant cancers
Eliminating protective autophagy in <i>KRAS</i>-mutant cancers, Published online: 01 April 2019; doi:10.1038/s41568-019-0137-5Two 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.
What’s driving T cell dysfunction?
What’s driving T cell dysfunction?, Published online: 01 April 2019; doi:10.1038/s41568-019-0138-4Failure 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.
Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data
Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data, Published online: 29 March 2019; doi:10.1038/s41568-019-0133-9This 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.
Overflow disrupts the genome
Overflow disrupts the genome, Published online: 29 March 2019; doi:10.1038/s41568-019-0136-6Hu 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.