Review Articles in 2024

Patient-derived xenograft (PDX) models are valuable surrogates for drug testing in precision oncology. In this Review, Welm and colleagues outline the opportunities and challenges of PDX models, discuss their relevance in functional precision oncology for replicating patient biology and share their perspective on how integrating these models with artificial intelligence can enhance their utility for personalizing cancer treatment.

Genetic predisposition is the major known cause of cancer in children and adolescents. In this Review, Kratz highlights the genetic architecture of cancer in children and adolescents, examining cancer predisposition syndromes, cancer predisposition genes, embryonic mosaicism and polygenic risk scores, focusing on their roles in cancer prediction, prevention, surveillance and therapy.

Androgen receptor (AR) signalling plays an important role in several cancers beyond prostate cancer. This Review highlights the context-dependent functions of AR in non-prostatic malignancies, examining the intrinsic function of AR in cancer cells and the tumour microenvironment, and summarizes ongoing AR-targeted clinical trials.

Chromothripsis is an extreme form of chromosome instability that causes the acquisition of multiple genomic aberrations. Simovic-Lorenz and Ernst discuss mechanistic models of chromothripsis and outline its role in cancer development and tumour evolution. Vulnerabilities of chromothriptic tumours that could be therapeutically exploited are also discussed.

In this Review, Wang and Zhang summarize the major findings of genetic and epigenetic association studies performed on cohorts of survivors of childhood cancer, which provide insights into the long-term adverse effects related to cancer therapy, and present suggestions for a future survivorship research strategy to inform precision survivorship care.

Immunotherapy shows promise in treating cancers by engineering T cells or using antibodies to activate them. However, cancer stem cells (CSCs) resist immunotherapies and drive cancer relapse. In this Review, Agudo and Miao highlight the mechanisms through which normal stem cells and CSCs in solid tumours achieve immune resistance, offering insights for the development of more effective cancer treatments.

In this Review, Hanahan et al. discuss how, in response to tumorigenesis, nearly all cell types in the tumour microenvironment can be programmed to mediate — as functionally distinct subtypes — immunosuppressive programmes that result in the inhibition of antitumour T cell activity and the evasion of immune destruction.

Understanding the early steps of cancer development is crucial for cancer prevention. In this Review, the authors summarize the advantages and limitations of clinical samples, autochthonous mouse models and organoid models, alongside advanced techniques such as direct imaging, lineage tracing and AI, to enhance understanding of early cancer progression.

Single-cell epigenomic technologies are refining our understanding of cancer evolution. Here Laisné et al. describe how epigenomic heterogeneity generates dynamic reservoirs of tumour cell states, through epigenomic reprogramming and selection among stochastic changes, which can be leveraged in the design of novel therapies.

Multiple myeloma is a plasma cell malignancy that is currently incurable. Cordas dos Santos et al. describe how multiple myeloma arises from precursor states and how T cell-redirecting therapies might be used to intercept disease progression at these earlier stages to improve patient outcomes.

In this Review, Rabas et al. describe the mechanisms by which primary tumours precondition distal organs to favour metastatic colonization — a limiting step of metastasis — and discuss how non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning, emphasizing the need for a holistic view to identify preventive or therapeutic opportunities.

In this Review, Linke, Munn and Jain provide a framework for understanding solid stress mechanobiology, examine the emerging and diverse roles of elevated compressive stresses in solid tumours, and highlight the potential for targeting mechanical abnormalities in cancer.

Metabolic disorders, such as obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes, are increasingly recognized as significant contributors to cancer development. Here, Taranto, Kloosterman and Akkari explore the influence of metabolic disorders on tumour progression through the metabolic interactions of macrophages and T cells to alter immune function and cancer outcomes.

In this Review, Arpinati et al. summarize how the extracellular matrix, produced primarily by cancer-associated fibroblasts, impacts tumour progression, metastasis and therapy response through modulation of T cell-mediated antitumour immunity and propose routes to target these mechanisms therapeutically.

Various strategies have been proposed and implemented to target the tumour vasculature, which supports tumour growth and progression. However, to date they have had variable success. Guelfi et al. describe some of these approaches and discuss how our increased understanding of the interactions between tumour vessels and the immune compartment could help generate combination therapies that provide durable responses in patients with cancer.

Transient ectopic lymphoid structures known as tertiary lymphoid structures (TLS) have been observed in many solid tumour types. In this Review, Teillaud et al. discuss how these TLS potentially orchestrate immune responses against tumours locally and are positively associated with prognosis and response to immune checkpoint inhibitors. The authors also outline how preclinical studies are highlighting the potential to manipulate the formation and function of TLS as a novel form of immunotherapy.

Circular RNAs, once considered by-products of splicing errors, are now accepted as key players in cancer biology. In this Review, Conn et al. review the functional interactome of circular RNAs in cancer, highlighting their contribution to oncogenesis, their potential as biomarkers and the prospect of leveraging them for novel therapeutics.

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.