Review Articles in 2021

This Review outlines our current understanding of the evolution and heterogeneity of pancreatic ductal adenocarcinoma (PDAC), which has advanced owing to the study of preclinical models and patient samples, and presents an evolutionary model of PDAC progression based primarily on genomics studies of human PDAC.

This Review discusses recent foundational and translational advances in gastric cancer genomics and epigenomics and highlights how these findings have improved our understanding of basic mechanisms driving gastric cancer biology as well as emerging preclinical targets.

This Review discusses the concept of transcription cycles in cancer, providing a framework for our understanding of dysregulated transcription in cancer and therapeutic targeting of dysregulated transcription cycles.

This Review discusses the context-dependent functions of transforming growth factor-β (TGFβ) with regard to the composition and behaviour of different cell populations in the tumour immune microenvironment, as well as emerging data that demonstrate that TGFβ inhibition can restore cancer immunity.

BH3-mimetic drugs have been designed to directly induce apoptosis in cancer cells by targeting prosurvival BCL-2 family proteins. This Review discusses their continued development and the challenges arising from their implementation in the clinic, such as resistance or on-target toxic effects, and the approaches that could be harnessed to overcome these obstacles.

This Review discusses the bone microenvironment and its impact on bone metastasis, defining a roadmap of the cancer cell journey through bone relative to various microenvironment components and in different cancer types as well as providing insight into new therapeutic targets.

This review discusses the immunosuppressive and tumour-promoting properties of microglia, monocyte-derived macrophage and astrocyte subsets in the brain tumour microenvironment, identifying new therapeutic opportunities for primary brain tumours and brain metastases.

This Review discusses the genomic evolution of Barrett’s oesophagus, which can sometimes progress to oesophageal adenocarcinoma (EAC). Understanding this evolution should improve early detection of EAC and may provide clues for the evolution of cancer more broadly.

Preclinical studies indicate that stress can promote tumour progression. However, in humans, stress-reducing interventions have yielded mixed effects on cancer mortality. This Review discusses multiple mechanisms identified in preclinical and clinical studies, and strategies to better study stress-reducing interventions clinically

Synthetic biomarkers are an emerging class of diagnostics that amplify disease signals for sensitive and specific detection of early-stage cancers. This Review discusses the rationale and design of biofluid-based synthetic biomarkers as well as translational challenges and future directions.

This Review discusses mechanistic links between fatty acid metabolism in cancer cells and disease behaviour and therapy resistance, integrating obesity-associated changes that modify cancer cell behaviour.

This Review discusses how fly tumours interact with the microenvironment and distant organs to influence disease progression and host physiology. The authors argue that the simplicity of flies and the ability to study lethality in this model provide an opportunity to address why patients ultimately die of cancer.

This Review describes the dynamic interplay between the DNA damage response and anticancer immunity, and highlights challenges and recent developments towards harnessing this interaction for therapeutic benefit.

The translational control of mRNAs during gene expression allows rapid, specific changes in the cell proteome. This Review describes the mechanisms underlying changes in mRNA translation in response to oncogenic signalling and microenvironmental stress, and how these changes can promote cancer onset, progression and resistance to anticancer therapies.

This Review introduces the latest advances in tissue clearing and three-dimensional imaging as applied to epithelial tissues, and explains how such techniques can improve both our understanding of tumour biology and cancer diagnostics.

This Review discusses the unique and complex immunological and metabolic features of the liver, from the precancerous stage through to oncological transformation and metastasis. Strategies for targeting this niche are also considered.

Mutational signatures can provide insights into the origins and vulnerabilities of specific cancers, and have potential for clinical utility. This Review highlights recent developments in the field, providing insights into practical issues and challenges in mutational signature analysis.

This Review examines the tissue-specific metabolism and associated therapeutic vulnerabilities of mutant KRAS-driven tumours, providing a comparative discussion of intrinsic metabolism, co-occurring mutations and metabolic interactions in the microenvironment in colorectal, lung and pancreatic cancer.

Despite the vast size of the non-coding genome, driver mutations in this space appear to be relatively infrequent. This Review highlights recent notable discoveries and challenges in the field of non-coding driver mutations, with a focus on somatic point mutations and indels.

The development of small-molecule degraders such as proteolysis-targeting chimeras (PROTACs) has made it possible to target oncoproteins previously considered undruggable. This Review discusses recent advances in the field, with a focus on opportunities and challenges for future development.