Perspectives

This Perspective proposes that data from multiple modalities, including molecular diagnostics, radiological and histological imaging and codified clinical data, should be integrated by multimodal machine learning models to advance the prognosis and treatment management of patients with cancer.

This Perspective discusses the main themes in cancer metabolism research that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing emerging aspects and questions that remain unanswered.

Collective cancer cell invasion with leader–follower organization is a key mechanism of metastasis, but a consensus definition of leader cell characteristics is lacking. This Perspective outlines a conceptual framework for understanding how leader cells coordinate the invasion process using a multitude of cellular and molecular programmes.

This Perspective highlights the importance of protein–protein interactions for the oncogenic functions of MYC and discusses how the MYC protein interactome might be exploited therapeutically.

This Perspective discusses the signalling programmes and biological factors that simultaneously induce cancer stem cells and reprogramme the immune response to facilitate tumour immune evasion. It also highlights therapeutic opportunities for simultaneous targeting of the cancer stem cell niche and immunosurveillance.

Disseminated leukaemia cells share many characteristics with metastasizing solid tumour cells. This Perspective discusses the key molecular processes that facilitate leukaemia metastasis, drawing comparisons with leukocyte trafficking and features of solid tumour invasion. Current and future strategies to target leukaemia metastasis are also discussed.

This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.

This Perspective outlines the connections of epithelial–mesenchymal transition programmes to the stem cell state in both normal and cancer stem cells and discusses emerging concepts related to the heterogeneous and plastic cell states generated by an epithelial–mesenchymal transition that influence our understanding of cancer stem cell biology and cancer metastasis.

The number of publications on deep learning for cancer diagnostics is rapidly increasing, but clinical translation is slow. This Perspective advocates performance estimation in external cohorts and strongly advises that a primary analysis is predefined in a standardized protocol preferentially stored in an online repository.

This Perspective discusses how therapeutic resistance is not only driven by genetic evolution but often involves non-genetic adaptive mechanisms that are intimately linked. Acknowledging these adaptive processes will enable the development of innovative strategies to monitor and counteract non-genetic therapy resistance as well as provide novel therapeutic avenues.

Metastatic dissemination can occur early during cancer progression, yet clinically overt metastases are often not detected for many years after surgical removal of the primary tumour. In this Perspective, Klein argues that understanding the ‘invisible’ phase of metastatic colonization is necessary to explain this phenomenon and develop better therapies to prevent metastasis.

This Perspective proposes operational definitions to define the hallmarks of cancer cell dormancy and, based on the latest evidence pertaining to the role of the microenvironment in regulating dormancy, presents key stages in the life cycle of a dormant cancer cell that could be targeted.

This Perspective advocates the study of tumour predisposition syndromes as an opportunity to better identify gene–environment interactions that influence cancer risk. Understanding syndrome-associated molecular mechanisms may provide new and more effective ways to prevent exposure-associated cancers in the general population.

This Perspective explores why TP53 is the most commonly mutated gene in cancer, discussing the evolutionary conservation of the p53 pathway in the context of tissue-specific functions and underlying reasons for the order of mutations which lead to p53-related cancer.

This Perspective discusses how executable computational models, integrating various data sets derived from preclinical models and cancer patients, can be used to represent the dynamic biological behaviours inherent in cancer. The article argues that these models might be used as patient avatars to improve personalized treatments.

This Perspective discusses the development of cachexia in the context of cancer progression, providing insight into how circulating factors contribute to this syndrome, and exploring how signals involved in metastasis can potentially amplify cachexia development.

This Perspective outlines our current understanding of how the bone marrow niche contributes to both the initiation and the progression of haematological malignancies and suggests guidelines for the field which might help to overcome existing research challenges.

This Perspective discusses the theory of multi-task evolution in cancer, which can contribute to understanding tumour diversity. It introduces the concept of generalist and specialist tumours in the contexts of driver mutations and discusses the potential applications to interpret intratumour heterogeneity.

This Perspective discusses how cell competition between tumour cells and neighbouring epithelial host cells may dictate tumorigenesis and proposes that manipulating the strength and direction of cell competition could form the basis of an orthogonal therapeutic strategy.

In this Perspectives article, the authors outline the preclinical and clinical evidence for epithelial–mesenchymal plasticity (EMP) in cancer progression and metastasis, focusing on recent challenges and controversies, and highlight strategies to therapeutically target the EMP process.