Evolutionary aspects of cancer resistance
Abstract
Humans are relatively cancer resistant, as judged by the absence of cancer in two thirds of the population. The susceptibility/resistance of other mammalians varies but shows no relationship to body size. Selection for longevity and cancer resistance may occur in parallel, as indicated by the extremely long lived and cancer free mole rat species. Microenvironmental control may play a major role in the defense against potential neoplastic cells. Our work confirms that normal fibroblasts inhibit the growth of tumor cells in vitro, largely by a contact dependent mechanism. The inhibitory capacity of the fibroblast differs depending on the site of origin, and is also different between normal and cancer derived stroma cells. Preliminary gene analysis points to major differences in gene expression in between inhibitory and non-inhibitory fibroblasts.
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Tumor-associated stroma actively facilitates tumor initiation, invasion, and therapeutic resistance through biochemical and biomechanical means.
“While stroma in normal tissues may possess anti-tumor properties, tumor-associated stroma—comprising cancer-associated fibroblasts, ECM, endothelial cells, and immune cells—actively facilitates tumor initiation, invasion, and therapeutic resistance [139,140,141,142].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [139]
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Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085 · see citing works
Tumor-associated fibroblasts predominantly come from local and not circulating precursors
Arina, A., Idel, C., Hyjek, E. M., Alegre, M.-L., Wang, Y., Bindokas, V. P., Weichselbaum, R. R., & Schreiber, H. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600363113 · Cited by 238 · see citing works
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“While stroma in normal tissues may possess anti-tumor properties, tumor-associated stroma—comprising cancer-associated fibroblasts, ECM, endothelial cells, and immune cells—actively facilitates tumor initiation, invasion, and therapeutic resistance [139–142].”
- Authors
- Klein, G.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Klein, George
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 25
- Pages
- 10-14
- ISSN
- 1044-579X (ISSN-L)
- OpenAlex
- W1995554689
- Cited by
- 32
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- tumor resistance, longevity, mole rats, tumor microenvironment, contact inhibition, tumor stroma, gene expression, cancer susceptibility
- MeSH terms
- Animals, Cell Adhesion, Cell Communication, Fibroblasts, Humans, Neoplasms, Oncogenes, Evolution, Molecular, Genetic Predisposition to Disease, Tumor Microenvironment
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