Articles in 2024

Conventional chemotherapy has successfully cured millions of patients with cancer, yet the mechanisms of action for this remain unclear. In this Perspective, Letai and de The assess the existing mechanisms proposed for the success of chemotherapy, identify gaps in our understanding and suggest principles for improving the utility of conventional chemotherapy to enhance treatment efficacy.

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.

Intercellular mitochondrial transfer via tunnelling nanotubes can influence cellular bioenergetics and function in tumours. A study in Cell demonstrates how this process can increase CD8⁺ T cell metabolic fitness and anti-tumour function.

Wang et al. demonstrate that lactate derived from glioblastoma stem cells, microglia and macrophages drives histone lactylation, activating immunosuppressive transcriptional programs and upregulating CD47, to suppress phagocytosis.

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.

In this Journal Club, Chakrabarti discusses a method to dissect the molecular architecture of inheritable gene expression (memory) states that mark cells that transition into drug-tolerant persister cells in melanoma.

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 Comment, Ben-Aharon et al. advocate for the creation of designated OncoYoung programs to address the unique needs of individuals with early-onset cancer, as well as multinational platforms with dedicated funding to investigate the aetiology of this disease and to develop preventive measures.

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.

The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.

Engel et al. conducted a genetic screen in which they identified the Fanconi anaemia (FA) pathway as a driver of chromothripsis, complex genomic rearrangements and generation of extrachromosomal DNA.

In this Journal Club, Chae and Chung discuss a study characterizing the differentiation and maturation of both tumour-resident and circulating B cells in patients with melanoma.

Ageing is a well-accepted risk factor for developing cancer. Yan et al. used a preclinical rat model to study the mechanisms facilitating the age-associated increase in breast tumorigenesis.

The Cancer Dependency Map (DepMap) is a data repository and research platform that can be utilized to systematically identify cancer vulnerabilities. Here Arafeh, Shibue et al. outline the current limitations and future strategies to enhance the DepMap project.

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.

In this Tools of the Trade article, Carly Tyer describes the development of Telo-seq, a method to enrich and sequence all telomeres within a sample, and highlights its use in distinguishing between the two telomere maintenance mechanisms used in cancer cells.

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.