Reviews & Analysis

In this Review, Harris et al. summarize the dynamic changes of the immune breast tumour microenvironment (TME) that take place during disease progression and in response to treatment, and outline emerging therapies to target the immune TME in patients with breast cancer.

In this Roadmap, Boire et al. consider the immediate causes of mortality in patients with cancer, a topic not often considered in either preclinical or clinical research, and provide recommendations for how we can stimulate research to advance our mechanistic understanding of these causes with a long-term view to improving the quality of life for patients with late-stage cancer.

Although there has been increasing interest in developing models that mimic the tumour microenvironment (TME), these models often fail to replicate the complex 3D fibre architectures observed in tumours. Here, Ashworth and Cox address this, discuss the current design and fabrication challenges, and outline state-of-the-art biomaterial technologies useful for recreating tissue-specific 3D architectures in vitro.

The tumour immune microenvironment greatly affects responses to immune checkpoint therapies. In this Perspective, Zemek et al. explore the dynamic changes in response to both immunotherapy and conventional treatment and advocate for strategic combination therapies over time to enhance antitumour immune responses.

Metastasis to the leptomeninges causes substantial neurological morbidity and mortality. Owing to the lack of mechanistic studies in this area, patients still face a bleak clinical prognosis. In this Review, Remsik and Boire provide a biology-focused overview of recent developments enabled by preclinical models and omics analyses and outline the need for further mechanistic research on leptomeningeal metastasis.

In this Perspective, Holder et al. discuss the limitations of current predictive biomarkers of response to immune checkpoint inhibitors and the need to further explore static, dynamic and patient-specific biomarkers using novel tools, such as machine learning and consortia-level initiatives.

This Review provides an introductory guide to artificial intelligence (AI)-based tools for non-computational cancer researchers. Here, Perez-Lopez et al. outline the general principles of AI for image analysis, natural language processing and drug discovery, as well as how researchers can get started with each of them.

In this Review, Paul et al. provide an overview of therapeutic antibodies as an important modality in cancer therapy today. They summarize the different approaches used by antibodies to target cancer cells including those of immune checkpoint inhibitors, bispecific antibodies and antibody–drug conjugates, as well as describing current strategies aimed at improving their efficacy and reducing toxicities.

In this Review, Zhang and colleagues provide an overview of the molecular characteristics of paediatric cancer and highlight how these malignancies arise from developmental aberrations resulting in paediatric-specific cancer genomes that influence both the initiation and progression of cancer. Additionally, they discuss genetic vulnerabilities within these cancer genomes that present opportunities for therapeutic interventions.

In this Review, Cichowski and colleagues provide an overview of combinatorial strategies designed to treat RAS-driven cancers that are based on four concepts that include vertical pathway inhibition, co-targeting RAS and adaptive survival pathways, co-targeting downstream or converging pathways and capitalizing on other cancer-associated vulnerabilities.

Tumour-associated lymphatic growth and remodelling were once viewed as a passive means by which cancer cells could regionally spread to lymph nodes. However, recent data point to an active and contrasting role for lymphatic vessels and their transport in antitumour immune surveillance. In this Review, Karakousi et al. provide a working framework to define this role for the lymphatic system in tumour progression and present avenues for its therapeutic manipulation to improve cancer immunotherapy.

Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.

In this Review, Meier et al. discuss the molecular mechanisms of necroptosis, delineate how this form of immunogenic cell death activates antitumour immune responses and explore the opportunities and limitations of targeting necroptosis for anticancer therapy.

This Review provides an overview of the complexity and significance of protein lipidation in cancer, outlines how targeting protein lipidation pathways offer promising avenues for developing cancer treatments, and discusses the current state of drugs targeting these pathways.

Extrachromosomal DNA (ecDNA) is now accepted as a major contributor to cancer pathogenesis. In this Review, Yan, Mischel and Chang highlight the recent advancements in ecDNA research, providing new insights into the biogenesis and maintenance of ecDNA, as well as its role in altering gene expression and promoting tumour heterogeneity.

In this Viewpoint article, we asked five Black cancer researchers and clinicians to present their ideas on how we can attract and retain more diverse researchers to the cancer community and how we begin to close the gap in cancer disparities.

In this Viewpoint article, we asked three scientists working on the cancer mycobiome to provide their opinions on advancements and challenges and what the future holds for this exciting field of cancer research.

In their Review article, Fuchs and colleagues discuss how a single or a few mutations in adult cells can lead to invasive cancers without a high mutational burden, demonstrating that non-genetic factors induce the epigenetic changes necessary for tumorigenesis.

In this Viewpoint, we asked four experts to discuss the increasing burden of cancer in low- and middle-income countries; they explore the changes that are necessary to improve cancer diagnosis, prevention and treatment within these nations.

In this Review, de Souza et al. discuss how advances in the ability to image protein markers at high-plex, at single-cell and even subcellular resolution, are expanding our understanding of tumour biology and clinical outcomes, and outline the future promise of combining such multiplex protein imaging methods with other forms of spatial omics.