Reviews & Analysis

This Perspective discusses the main themes in cancer metabolism research that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing emerging aspects and questions that remain unanswered.

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.

Collective cancer cell invasion with leader–follower organization is a key mechanism of metastasis, but a consensus definition of leader cell characteristics is lacking. This Perspective outlines a conceptual framework for understanding how leader cells coordinate the invasion process using a multitude of cellular and molecular programmes.

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.

Based on a virtual discussion during the American Association for Cancer Research (AACR) 2020 Annual Meeting, we asked several scientists actively working to improve representation of Black American populations in cancer research how they are addressing these issues.

This Perspective highlights the importance of protein–protein interactions for the oncogenic functions of MYC and discusses how the MYC protein interactome might be exploited therapeutically.

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.

This Perspective discusses the signalling programmes and biological factors that simultaneously induce cancer stem cells and reprogramme the immune response to facilitate tumour immune evasion. It also highlights therapeutic opportunities for simultaneous targeting of the cancer stem cell niche and immunosurveillance.

This Review provides an update of interleukins in tumour biology, covering the milestones of the latest discoveries of interleukin-related mechanisms in cancer, together with their application in clinical practice. It includes an overview of current clinical trials and breakthrough preclinical concepts.

Variation in mitochondrial DNA (mtDNA) is common in certain tumours. This Review discusses the relevance of heritable, somatic and ancient mtDNA variants to cancer and how subtle changes in mtDNA result in metabolic, epigenetic and transcriptional changes that affect carcinogenesis.

Deregulation of chromatin modification underlies a myriad of oncogenic processes. This Review synthesizes the many connections between chromatin modifications and cancer, discussing recent advances and highlighting options for therapeutic targeting.

Disseminated leukaemia cells share many characteristics with metastasizing solid tumour cells. This Perspective discusses the key molecular processes that facilitate leukaemia metastasis, drawing comparisons with leukocyte trafficking and features of solid tumour invasion. Current and future strategies to target leukaemia metastasis are also discussed.

This Review discusses how long noncoding RNAs influence metastasis by functioning in discrete pro-metastatic steps including the epithelial–mesenchymal transition, invasion and migration and organotrophic colonization, and by influencing the tumour microenvironment. Diagnostic and therapeutic potential as well as controversies and ongoing technical challenges are discussed.

This Review broadly discusses therapeutic cancer vaccines, covering resistance mechanisms and strategies to overcome these, how to improve the antigen repertoire for vaccines and vaccine platforms, and approaches for enhancing immunotherapy efficacy.

This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.

An improved understanding of tumour immunology and therapy must assess the systemic immune landscape beyond the tumour microenvironment. This Review outlines peripheral immune cell reorganization in response to tumour growth and therapy, their contribution to immunotherapy responses and their potential as diagnostic or predictive biomarkers.

Autophagy is induced by stress signals in cancer cells as well as immune cells in the tumour microenvironment. This Review discusses how autophagy modulates antitumour immunity in cancer cell autonomous and non-autonomous ways, and potential approaches for targeting autophagy to enhance the antitumour immune response.

Focal adhesion kinase (FAK) is overexpressed in many cancers and is involved in a multitude of oncogenic processes and resistance mechanisms. This Review discusses the rationale and preclinical evidence for FAK-based combination therapies and strategies for future development.

This Review discusses the role of functional (impacting tumour phenotype) and non-functional intra-tumour heterogeneity (ITH) in cancer evolution, highlighting the importance of considering genetic and non-genetic factors and their impact on patient outcomes.

Immune checkpoint inhibition does not benefit all patients. This Review discusses how antigen presentation, which is crucial for the success of this therapy, may be disrupted in tumours and dendritic cells of patients, and how tumours may further evade natural killer cell recognition.