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Genomic control of metastasis

Published version
Peer-reviewed

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Authors

Patel, Saroor A. 
Rodrigues, Paulo 
Wesolowski, Ludovic 

Abstract

Abstract: Metastasis remains the leading cause of cancer-associated mortality, and a detailed understanding of the metastatic process could suggest new therapeutic avenues. However, how metastatic phenotypes arise at the genomic level has remained a major open question in cancer biology. Comparative genetic studies of primary and metastatic cancers have revealed a complex picture of metastatic evolution with diverse temporal patterns and trajectories to dissemination. Whole-genome amplification is associated with metastatic cancer clones, but no metastasis-exclusive driver mutations have emerged. Instead, genetically activated oncogenic pathways that drive tumour initiation and early progression acquire metastatic traits by co-opting physiological programmes from stem cell, developmental and regenerative pathways. The functional consequences of oncogenic driver mutations therefore change via epigenetic mechanisms to promote metastasis. Increasing evidence is starting to uncover the molecular mechanisms that determine how specific oncogenic drivers interact with various physiological programmes, and what triggers their activation in support of metastasis. Detailed insight into the mechanisms that control metastasis is likely to reveal novel opportunities for intervention at different stages of metastatic progression.

Description

Keywords

Review Article, /631/67/322, /631/67/68, review-article

Journal Title

British Journal of Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

124

Publisher

Nature Publishing Group UK
Sponsorship
RCUK | Medical Research Council (MRC) (MC_UU_12022/7)