Clonal heterogeneity and tumor evolution: past, present, and the future

McGranahan, Nicholas; Swanton, Charles

doi:10.1016/j.cell.2017.01.018

Cited by 2,840Cancer Genomics and DiagnosticsCancer Cells and MetastasisEvolution and Genetic Dynamics

Clonal heterogeneity and tumor evolution: past, present, and the future

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McGranahan, Nicholas, Swanton, Charles·2017·Cell

DOI 10.1016/j.cell.2017.01.018

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Abstract

Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome.

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Authors: McGranahan, N., & Swanton, C.
Affiliations: The Francis Crick Institute (GB)
University College London Hospitals NHS Foundation Trust (GB)
Corresponding author: Swanton, Charles
ORCID: McGranahan, Nicholas
Swanton, Charles
Venue: Cell
Publisher: Elsevier BV
Published: 2017-02
Volume: 168
Issue: 4
Pages: 613-628
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2017.01.018
OpenAlex: W2586629973
Cited by: 2,840
References: 165
Citations by year: 2026: 320 · 2025: 279 · 2024: 295 · 2023: 331 · 2022: 368 · 2021: 345 · 2020: 327 · 2019: 273 · 2018: 224 · 2017: 77 · 2016: 1
FWCI: 25.29
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Cancer Research UK (23896, 20466, 17786)
Rosetrees Trust
Novo Nordisk Fonden (NNF15OC0016584)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords: intratumoral heterogeneity, tumor evolution, clonal heterogeneity, chromosomal abnormalities, metastasis, tumor microenvironment, drug resistance, immune microenvironment, clinical trial design, anticancer drug development
MeSH terms: Animals, Humans, Mutation, Neoplasms, Genetic Heterogeneity, Drug Resistance, Neoplasm, Genomic Instability

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Clonal heterogeneity and tumor evolution: past, present, and the future

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