Origins of Metastatic Traits
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How cancer cells acquire the competence to colonize distant organs remains a central question in cancer biology. Tumors can release large numbers of cancer cells into the circulation, but only a small proportion of these cells survive on infiltrating distant organs and even fewer form clinically meaningful metastases. During the past decade, many predictive gene signatures and specific mediators of metastasis have been identified, yet how cancer cells acquire these traits has remained obscure. Recent experimental work and high-resolution sequencing of human tissues have started to reveal the molecular and tumor evolutionary principles that underlie the emergence of metastatic traits.
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Cancer stem cells are thought to be resistant to targeted therapies and responsible for metastasis, disease recurrence and poor outcomes.
“Cancer stem cells (CSCs) are thought to be resistant to targeted therapies and responsible for metastasis, disease recurrence and poor outcomes [42, 45].”
From An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy (2022) · cites this paper as [42]
In “Sources of Influence: Germline, Plasticity, Stroma, and Therapy” (page unavailable), the review says a more stem-like phenotype may help cells through metastatic bottlenecks and that EMT has been proposed to confer stemness and therapy resistance together. It does not specifically establish CSC resistance to targeted therapies or attribute disease recurrence and poor outcomes to CSCs. “Metastasis Bottlenecks” (page unavailable) also cautions that individually circulating CSCs would probably not form metastases. (LLM, conf=0.86)
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Metabolic reprogramming and cancer progression
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- Authors
- Vanharanta, S., & Massagué, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Massagué, Joan
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 24
- Issue
- 4
- Pages
- 410-421
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3998120
- OpenAlex
- W2071732560
- Cited by
- 563
- References
- 132
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 54 · 2023: 43 · 2022: 35 · 2021: 57 · 2020: 54 · 2019: 48 · 2018: 63 · 2017: 51 · 2016: 53 · 2015: 49 · 2014: 23
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- National Institutes of Health
- U.S. Public Health Service (U54-163167)
- Medical Research Council (MC_UU_12022/7)
- National Cancer Institute (P01-CA94060, R37-CA34610, R37CA034610, P01CA129243, P01CA094060, U54CA163167, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- metastasis, tumor evolution, cancer cell dissemination, tumor heterogeneity, cancer genomics
- MeSH terms
- Animals, Breast Neoplasms, Cell Transformation, Neoplastic, Disease Models, Animal, Female, Humans, Male, Neoplasm Metastasis, Phenotype, Prostatic Neoplasms, Stochastic Processes, Disease Progression, Mice
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