Reviews & Analysis

This Review outlines risk factors and prevention strategies for cutaneous squamous cell carcinoma (cSCC) and highlights recent advances in the understanding of the impact of molecular and cellular intra-tumour heterogeneity that provide the basis for new therapeutic strategies to treat advanced cSCC.

In this Perspective article, Mel Greaves and co-workers outline emerging evidence that suggests that children with newly diagnosed acute lymphoblastic leukaemia may have a delayed maturation of the gut microbiome compared with healthy children, a deficit that might be associated with early-life epidemiological factors and could contribute to the risk of transformation of preleukaemic clones in response to common infectious triggers.

In this Perspective, the authors suggest that different tumour microenvironments have ‘archetypal’ qualities across all cancers — characteristic and repeating collections of cells and gene-expression profiles at the level of the bulk tumour. They propose the existence of 12 dominant immune archetypes.

In this Review, Schwenck et al. discuss how PET imaging of cancer has advanced through its combination with CT and MRI and the development of an array of imaging probes, and how these innovations now need to be fully integrated into the clinic to improve cancer diagnostics and guide therapy.

In this Review, Banushi et al. discuss how endocytotic pathways impact many cancer processes including nutrient scavenging, metastasis and therapeutic drug delivery, and how knowledge of these pathways can be used to improve cancer therapy in the clinic.

Eukaryotic initiation factor 4F (eIF4F) controls the translation of a subset of transcripts that include those encoding oncogenic proteins. In this Perspective article, Bartish et al. discuss the implications of targeting eIF4F on immune and stromal cells in the tumour microenvironment. In addition to discussing data from cancer models, the authors incorporate extensive data from non-cancer contexts to identify potential desirable or unwanted effects of eIF4F inhibition in these cells.

Although metastasis is the leading cause of cancer-related deaths, our understanding of the process is limited. In this Review, Hebert et al. discuss the key features of various models of metastasis, highlighting their advantages and disadvantages for further dissecting mechanisms of metastasis and developing metastasis-targeted therapies.

This Review outlines how the developmental pathways that are involved in melanocyte development and skin pigmentation are highjacked by melanoma cells to drive melanomagenesis, progression and therapy resistance.

Ruf et al. discuss the emerging roles of innate lymphoid cells and innate-like T cells in cancer immunity. The authors highlight their role in bridging adaptive and innate immunity, as well as their potential as immunotherapeutic targets.

Knowledge of the native T cell landscape and how it evolves under immunotherapeutic pressure will enable us to improve upon current clinical responses to immune-based interventions. In this Review, Oliveira and Wu outline how recent multidimensional single-cell studies have brought us a step closer to this goal by linking intratumoural phenotypes with the antigen specificity of T cells.

In this Perspective, Magnon and Hondermarck introduce the emerging field of cancer neuroscience and outline how the bidirectional crosstalk between the brain and peripheral tumours drives cancer development and progression.

Overactive nucleotide synthesis is a hallmark of cancers and inhibitors of nucleotide synthesis pathways have shown promise in some cancer types. In this Review, Mullen and Singh give an overview of the role of aberrant nucleotide synthesis in supporting cancer cell growth, immune evasion, metastasis and resistance to cancer therapies, with a focus on identifying opportunities for the use of combination therapies to target these pathways more effectively.

Fibrolamellar hepatocellular carcinoma is a rare cancer type and, as such, research into this disease comes with many challenges. In this Perspective, Sanford Simon tells of his personal journey and experiences in the fight against this rare cancer type.

In this Perspective, Tsoumakidou explores the emerging role of cancer-associated fibroblasts as positive regulators of the adaptive immune system in cancer.

Clinical correlative data and a plethora of preclinical studies of cancers have shown that both tumour-associated and metastasis-associated macrophages play an important role in promoting cancer. In this Perspective article, Cassetta and Pollard chronologically explore the evolution of our understanding of tumour-associated macrophage biology and enabling technologies.

Myeloid cells in the tumour microenvironment strongly influence tumour progression, and targeting these cells has been a key clinical focus. In this Review, Barry et al. discuss preclinical and clinical data on myeloid-targeting therapies, with a focus on how understanding context-specific effects might aid the design of successful clinical trials for these drugs.

This Review outlines how the profound intertumoural heterogeneity in immune landscapes of tumours is shaped by cancer cell-intrinsic alterations and highlights how the crosstalk between these two continuously evolving systems not only challenges therapy success of immunomodulatory drugs but also provides the basis for new therapeutic strategies to overcome immune evasion.

Acetyl coenzyme A (acetyl-CoA) is a key metabolite in carbohydrate and lipid metabolism and plays a role in signalling through protein acetylation, and the dysregulation of these pathways is a hallmark of various cancers. In this Review, Guertin and Wellen give an overview of acetyl-CoA metabolism in health and in cancer and discuss emerging therapeutic strategies for targeting metabolic pathways involving acetyl-CoA.

This Review discusses the diverse ways in which cancer-associated RNA splicing dysregulation promotes tumour initiation and progression, existing and emerging approaches for targeting splicing for cancer therapy and outstanding questions and challenges in the field.

Reprogrammed metabolism is a hallmark of cancer. Here, Li, Zhang and colleagues describe how signal transducer and activator of transcription (STAT) proteins alter cancer cell metabolism by sensing and transducing signals from the tumour environment and modulating signalling pathways, transcription factors, mitochondrial proteins and enzymes.