Review Articles

Adoptive cell therapies have emerged as promising approaches for the treatment of patients with cancer. Engineering cell therapies to confer resistance to small-molecule therapies, chemotherapies and antibody-based therapies will improve their utility and success. Here, Wellhausen, Baek and colleagues outline the key principles of engineering resistance and potential applications for haematopoietic stem cell transplantation and allogeneic immune cell therapies.

Despite the success of immune-checkpoint inhibitors, many patients are at risk of developing immune-related adverse events. One of these is myocarditis or inflammation of the heart. Munir, Gutierrez and colleagues describe the data from preclinical models and patient samples, which have begun to provide a mechanistic understanding of myocarditis resulting from immune-checkpoint inhibitors, and present suggestions for improving both the diagnosis and treatment of patients experiencing this immune-related toxicity.

In this Review, Polak, Zhang and Kuo discuss the currently available and rapidly evolving 3D tumour organoid models that capture the tumour immune microenvironment. They highlight opportunities for organoid-based investigations of tumour immunity, drug development and precision medicine.

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.

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.

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.

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.

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 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 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.

Although p53 was once considered undruggable, in this Review, Peuget et al. discuss the progress made in targeting p53 as a form of cancer therapy with approaches ranging from restoration of mutant p53 function to inhibition of the negative regulator of p53, MDM2, as well as newer strategies, including p53-based mRNA vaccines and antibodies.

Transposable elements, also known as junk DNA, constitute nearly half of the human genome. This Review by Liang et al. discusses how tumours exploit these transposable elements during their evolution but also how they represent a vulnerability that could be targeted through immunotherapeutic approaches.

Although hyperactivation of BRAF has been well-established to drive tumour progression and drug resistance, the role of CRAF in cancer is becoming increasingly relevant. Here, Riaud et al. summarize the various oncogenic roles of CRAF and the potential for CRAF-targeted therapies to improve the clinical outcome for RAF1 altered tumours.

In this Review, Sato and colleagues provide an overview of the clinicopathological and phenotypical impact of lineage commitment and plasticity during tumorigenesis and progression of human epithelial cancer and discuss the molecular mechanisms that underlie histological lineage transition.