Reviews & Analysis

Human germ cell tumours are a heterogeneous group of neoplasms that occur in the gonads and extragonadal sites along the midline of the body. This Review outlines a developmental pathogenetic model for the origin of all germ cell tumours, which is based on the unscheduled reprogramming of cells of the early embryo and germ line.

Co-occurring genomic alterations contribute to the heterogeneity of driver oncogene-defined non-small-cell lung cancer subgroups. This Review discusses the effects of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer.

Endometrial cancer is histologically and molecularly complex, and effective clinical strategies for aggressive forms of the disease are needed. This Review discusses the identification and potential use of molecular features of endometrial cancer for early detection, treatment and risk stratification.

In this Viewpoint, we have asked recipients of the Nature Awards for Mentoring in Science about their views on good mentoring, and how mentorship can help to achieve a positive research culture and contribute to scientific discovery in cancer research.

Paediatric solid tumours are known to be divergent from adult malignancies. This Review describes the molecular landscape of paediatric solid tumours, the therapeutic vulnerabilities that can be targeted and the preclinical models available to test the efficacy of investigational drugs with a view to accelerating translational progress.

To date, very few actionable tumour-specific antigens (TSAs) have been identified that have successfully translated into therapeutic cancer vaccines. This Opinion article provides both examples of TSAs alternative to the traditional single-nucleotide variant neoantigens and details about the novel computational tools used to identify them, with the view to broaden the number of targetable antigens that can be used for cancer vaccine development.

The transcriptional activators YAP and TAZ have been discussed mainly for their cell-autonomous functions in cancer. Recent studies suggest their emerging roles in orchestrating tumour–stroma interactions, acting as a signalling hub, as discussed in this Review article.

This Review discusses the diverse effects of senescence and the senescence-associated secretory phenotype (SASP) on tumour growth, focusing on the functional and sometimes opposing outputs of the SASP in stromal cells and incipient tumour cells.

Therapeutic strategies in malignant melanoma are challenged by resistance mechanisms that are based on phenotype plasticity. This Review discusses different phenotypes in melanoma, how they are controlled and how phenotype plasticity contributes to melanoma progression and therapy resistance.

This Review discusses the rapidly accumulating preclinical evidence in support of antitumour, but also of some pro-tumour, roles for γδ T cells in cancer progression. It also outlines the potential for manipulating their functions for use as an unconventional form of cancer immunotherapy.

In this Viewpoint article, we asked four scientists working on the cancer microbiome to provide their opinions on the current state of the field, where the research is heading and the challenges of implementing this field for clinical utility.

This Opinion article provides an overview of the mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour progression.

Tertiary lymphoid structures (TLSs) form outside of lymphoid tissues at sites of chronic inflammation, including tumours. This Review describes the evidence demonstrating that TLSs are critical for generating antitumour immune responses and are associated with better prognosis in certain cancer types. It also presents potential strategies aimed at inducing TLS neogenesis to improve clinical responses in poorly immunogenic cancers.

For any given cancer type, there are patients who have exceptionally favourable or atypically poor responses to treatment and overall survival. This Opinion article outlines approaches to identify and study these patients at the extremes of the spectrum with a view to gain insights that will be applicable to the wider patient population.

Alterations of the cyclin-dependent kinase (CDK)–RB–E2F axis occur in virtually all cancers and result in heightened oncogenic E2F activity and uncontrolled proliferation. This Review discusses the activities of E2F proteins in cancer and therapeutic strategies to target this oncogenic pathway.

The implementation of screening tests for certain cancers has led to the phenomenon of overdiagnosis, whereby a cancer is diagnosed that would otherwise not go on to cause symptoms or death. This Opinion article discusses the effects of overdiagnosis and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour biology and the tumour microenvironment.

This Opinion discusses three different mechanisms by which high-dose vitamin C can be selectively toxic to cancer cells. These findings from preclinical studies will be beneficial for the design of clinical trials testing high-dose vitamin C as an anticancer therapy.

Recurrent oncogenic chromosomal rearrangements frequently involve genes required for chromatin regulation and transcriptional control. This Review discusses mechanistic insights into the chromatin-based functions of many of these oncogenic fusion proteins that are guiding the design of new therapeutic approaches.

This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.

The existence of extrachromosomal DNA (ecDNA) in cancer was first described decades ago, but recent reports of oncogene amplification on ecDNA have reinvigorated interest in this field. This Perspectives article discusses the potential implications of oncogene amplification on ecDNA in cancer.