Reviews & Analysis

As well-established players in the metastatic cascade, circulating tumour cells (CTCs) hold promise for improved cancer diagnosis and disease monitoring. In this Review, Ring et al. overview the current understanding of CTC biology, highlighting specific opportunities and vulnerabilities for future CTC-focused therapies.

Genes encoding DNA damage response factors are frequently mutated in cancer, causing genomic instability and presenting opportunities for therapeutic intervention. This Review discusses state-of-the-art strategies for DNA damage response inactivation using small-molecule inhibitors.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and its incidence continues to rise, mostly owing to an increase in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. In this Review, the authors describe HPV-positive and HPV-negative HNSCC tumour microenvironments and discuss current and novel treatment modalities.

Pancreatic ductal adenocarcinomas are characterized by a robust stromal reaction. This Review discusses how the evolution of the epithelium in pancreatic cancers is coordinated with a programme of stromal progression; this comprehensive picture of tumour development might, in turn, point to new therapeutic vulnerabilities.

In this Perspective, Wahida et al. consider six riddles in precision oncology that must be solved to achieve better clinical responses to molecular targeted therapies.

This Review covers recent advances in intravital imaging of mammalian models of cancer and describes how intravital imaging can help to understand the role of the tumour microenvironment in cancer progression and metastasis, and to develop novel treatments and therapies.

The activation of DNA damage tolerance (DDT) pathways as part of the replication stress response to DNA damage is key for maintaining genome integrity and, as a result, these pathways are closely linked to tumorigenesis. In this Review, Cybulla and Vindigni discuss the many connections between DDT, replication stress and cancer, detail opportunities for clinical biomarker development, and outline therapeutic strategies for targeting these pathways.

Three-dimensional bioprinted cancer models could revolutionize understanding and treatment of cancer. Neufeld, Yeini and Pozzi discuss how such models can reveal novel biomarkers and drug targets, illuminate mechanisms of tumorigenesis and interactions between tumour, stromal and immune cells, and advance personalized cancer therapy.

‘Ductal carcinoma in situ’ (DCIS) describes abnormal cells in the milk ducts. DCIS is often non-invasive, although a small proportion of cases leave the ducts and progress to invasive breast cancer. This Review discusses the existing data for distinguishing progressive and non-progressive DCIS, with a focus on informing current disease management strategies.

The gut microbiota has been shown to regulate responses to various cancer therapies, and the microbial species involved and their underlying mechanisms have begun to be unravelled. In this Perspective, Fernandes and colleagues present this evidence and then outline how it could be used to develop microbiota-based therapies for patients with cancer.

This Perspective outlines the preclinical emergence of smart cell therapeutics, which when paired with machine learning analysis of genomic data could be implemented in the clinic to both enhance tumour recognition and prevent tumour escape.

Clinical trials of immunotherapies have so far failed to demonstrate efficacy in high-grade serous ovarian cancers. Here, Kandalaft et al. classify high-grade serous ovarian cancers into distinct immunophenotypes that might account for these failures and could also provide a rational basis for tailored immunotherapy in the future.

The increasing size of cancer datasets requires new ways of thinking for analysing and integrating these data. In this Review, Jiang et al. discuss considerations and strategies for wielding ‘big data’ ― large, information-rich datasets ― in basic research and for translational applications such as identifying biomarkers, informing clinical trials and developing new assays and treatments.

Malignant cells show uninhibited proliferation and cellular plasticity, features also reminiscent of embryogenesis. In this Perspective, Sharma and colleagues present their oncofetal ecosystem concept, discuss evidence of oncofetal reprogramming in malignant and non-malignant cells, and debate the therapeutic relevance of these findings.

This Review describes how advances in lentiviral-based cellular barcoding techniques, including both genetic and optical barcoding, have enabled the spatiotemporal fate of individual cancer cells and their progeny to be tracked, providing valuable information for biological discovery and possible clinical translation.

In this Viewpoint article, we asked four scientists working in the field of cancer nanomedicine to provide their opinions on how we can truly fulfil the great promise of nanotechnologies for the detection, diagnosis and treatment of patients with cancer.

This review gives an overview of natural killer (NK) cell-based immunotherapies. The authors describe the various engineering strategies used to increase NK cell cytotoxicity and persistence, as well as the current challenges and opportunities for the future design of next-generation NK cell therapies.

Environmental exposure to aristolochic acid-containing plant material and its use in traditional medicines have been linked to a wide range of cancers. In this Review, Das et al. describe the evidence for aristolochic acid as a potent carcinogen and explore the impact of public health measures on preventing aristolochic acid-linked cancers and nephropathy, with a call to action for the implementation of further preventative measures.

Cancer cells use telomere-maintenance mechanisms to achieve replicative immortality. This Review describes these mechanisms — telomerase and the ALT pathway — and the recent developments in targeting them as therapeutic strategies for patients with cancer.

Structural variations (SVs), which comprise genome-level aneuploidies and rearrangements, result in both copy number changes and novel interactions between formerly distant genomic elements. This Perspective discusses how the folding of the 3D genome, and differences in its folding across cell types, affect the formation of SVs and their impact on cancer cell fitness in different cancer types.