Perspectives in 2020

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.