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Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

microRNAs have recently been shown to affect diverse processes involved in metastasis. How do microRNAs interfere with or promote metastasis, could they be used as predictive markers, and are they possible therapeutic targets?

Non-coding RNAs (ncRNAs) are involved in the development of a number of diseases, including cancer, and the first ncRNA-targeted therapeutics have recently entered clinical trials. Here, Calin, Ling and Fabbri present the latest insights into ncRNA biology, with a focus on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and discuss how these inform therapeutic strategies that modulate ncRNAs in cancer.

T-UCRs encode long non-coding RNAs implicated in human carcinogenesis, but the underlying mechanisms are poorly understood. Here, the authors identify uc.339 as an oncogene in lung cancer that is upregulated through the loss of TP53 and promotes Cyclin E activation by entrapping regulatory miRNAs.

MicroRNAs (miRNAs) is an exciting and fast-moving field in cancer diagnosis and therapeutics. This Review highlights the use of circulating miRNAs in body fluids as a noninvasive diagnostic tool and as a treatment-response predictor. It also explores the concept that body-fluid-based miRNAs possibly originated as the first 'hormones'.

In melanoma, reduced ADAR1 impairs A-to-I microRNA editing. Here, the authors show that miR-378a-3p undergoes this editing in non-metastatic cells and the edited form of miR-378a-3p binds to the PARVA oncogene, inhibiting its expression and preventing melanoma progression and metastasis.

Changes in the expression of the RNA-binding protein HuR are common in several cancers. Here, the authors show that HuR regulates glutaminase mRNA metabolism in the context of breast cancer. This work reveals that dual inhibition of HuR and glutaminase may have therapeutic potential.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

MicroRNAs from head and neck cancer cells, shuttled to sensory neurons by extracellular vesicles, cause a shift to an adrenergic neuronal phenotype that promotes tumour progression.

The transcription factor ΔNp63 is a master regulator of epithelial development and integrity of stratified epithelial tissues. Here, the authors unveiled the lncRNA NEAT1 as an additional player of the highly complex regulatory network by which ΔNp63 controls epidermal homeostasis.

A mathematical model of the time course of tumour responses to immunotherapy predicts tumour burden and treatment sensitivity across cancer types and drug combinations.

Ovarian cancer is often accompanied by metastases at the time of diagnosis and has a poor survival rate. In this study, Aslan et al.identify a role for ZNF304 in ovarian cancer metastasis and show that the protein transcriptionally regulates β1 integrin, resulting in a reduction in programmed cell death.

Single-cell analysis of gastric cancer samples tracks the cell of origin of metastatic lesions and identifies an independent prognostic signature of the clinical outcome.

The mechanisms underlying resistance to immunotherapy are still poorly understood. Here, the authors show that BMP7, a molecule part of the TGF-beta superfamily, suppresses proinflammatory antitumor responses and may represent a target for overcoming resistance to PD1 inhibitors.

Over the past decade, several RNA-based therapies have gained FDA approval. Additional noncoding RNA (ncRNA)-based therapeutic approaches — targeting microRNAs and long ncRNAs — are now also gaining interest. Here, Calin and co-authors assess the hurdles facing the clinical translation of ncRNA-based therapeutics and highlight promising emerging solutions to address these issues.

The microRNA-200 family members have a role in regulating tumour angiogenesis but the underlying mechanism is unclear. In this study, Pecot et al.demonstrate that miR-200 affects angiogenesis by altering endothelial and cancer cell cytokine secretion.

MicroRNAs play important roles in the maintenance of cellular homeostasis through the post-transcriptional regulation of gene expression. Here, the authors implicate loss of the miRNA biogenesis factor Drosha and altered miRNA maturation in tumour progression under hypoxic conditions.

TRPA1 has been reported to contribute lung cancer adenocarcinoma (LUAD), but the mechanisms are unclear. Here the authors propose that TRPA1/FGFR2 interaction is functional in LUAD and show that astrocytes oppose brain metastasis by mediating the downregulation of TRPA1 through exosome-delivered miRNA-142-3p.

Bar-Eli and colleagues report that CREB-mediated downregulation of the RNA-editing enzyme ADAR1 results in decreased adenosine-to-inosine editing of miR-455-5p, which enhances melanoma growth and metastasis.

Understanding the mechanisms by which tumour cells adapt or succumb to targeted therapies is crucial to improving cancer treatment. A study in this issue of Nature Metabolism demonstrates how microRNAs, metabolic pathways and pseudohypoxia play a major role in the drug tolerance to epidermal growth factor receptor (EGFR) inhibitors in lung adenocarcinoma.

The discovery of miRNAs in body fluids has opened up the possibility of using them as non-invasive biomarkers in cancer detection and as predictors of therapy response in cancer treatment. This Review article considers the latest developments in the use of circulating microRNAs as prognostic and predictive biomarkers and discusses their utility in personalized medicine.

Research on microRNAs in cancer is moving apace. This Review discusses why miRNA profiling is proving to be a useful new tool for identifying tumour subtypes, and can accurately predict patient outcome. Could miRNAs be exploited to treat tumours?

Manel Esteller and colleagues report truncating mutations in TARBP2, an integral component of a DICER1-containing complex, in human colorectal cancers. This is the first report of a mutation in one of the genes involved in miRNA processing in human cancer.

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers.

In this Review, the authors describe our current knowledge of the role of microRNAs, long non-coding RNAs and circular RNAs in disease, with a focus on cardiovascular, neurological, infectious diseases and cancer. Further, they discuss the potential use of non-coding RNAs as disease biomarkers and as therapeutic targets.

Evidence of the functional roles of non-coding RNAs in cancer is expanding, and the potential of these RNAs as diagnostic and prognostic biomarkers is increasingly recognized. Herein, the authors review the recent developments in these areas and provide compendiums of circulating microRNAs and long non-coding RNAs that have promise as diagnostic and prognostic cancer biomarkers.