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How the ageing microenvironment influences tumour progression
Open accessAbstract
Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health problem. It is estimated that, by 2050, more than 20% of the world's population will be over the age of 60 - the economic, healthcare and financial burdens this may place on society are far from trivial. In this Review, we address the role of the ageing microenvironment in the promotion of tumour progression. Specifically, we discuss the cellular and molecular changes in non-cancerous cells during ageing, and how these may contribute towards a tumour permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. We also discuss the contribution of these changes to responses to cancer therapy as ageing predicts outcomes of therapy, including survival. Yet, in preclinical studies, the contribution of the aged microenvironment to therapy response is largely ignored, with most studies designed in 8-week-old mice rather than older mice that reflect an age appropriate to the disease being modelled. This may explain, in part, the failure of many successful preclinical therapies upon their translation to the clinic. Overall, the intention of this Review is to provide an overview of the interplay that occurs between ageing cell types in the microenvironment and cancer cells and how this is likely to impact tumour metastasis and therapy response.
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“In addition to the accumulation of genomic mutations over time, age-related cellular senescence also contributes to cancer development and progression (2).”
From Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment (2023) · cites this paper as [2]
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“SASP has been linked to the aggressiveness of certain cancers (2, 10).”
From Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment (2023) · cites this paper as [2]
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“However, the main obstacle to achieving efficacious immunotherapy is the tumor microenvironment (TME), which may accelerate senescence of the immune system [18, 19]: potential targets for rejuvenating the immune system are still a hypothesis.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [18]
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“Furthermore, in aging TME, changes in immune cell function and secretion of SASP molecules dramatically affect tumor progression [18].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [18]
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“Finally, emerging evidence suggests that the aging microenvironment largely contributes to age-related decline in immune function and may also provide potential targets for rejuvenating the immune system [18].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [18]
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“as well as due to biophysical alterations of the extracellular matrix that affect the mobility and placement of immune effectors.261”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [261]
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Metadata
- Authors
- Fane, M., & Weeraratna, A. T.
- Affiliations
- The Wistar Institute (US)
- Corresponding author
- Fane, Mitchell
- Weeraratna, Ashani T.
- Venue
- Nature Reviews Cancer
- Published
- 2019-12-13
- Volume
- 20
- Issue
- 2
- Pages
- 89-106
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC7377404
- OpenAlex
- W2995607278
- Cited by
- 849
- References
- 228
- Citations by year
- 2026: 109 · 2025: 176 · 2024: 166 · 2023: 130 · 2022: 122 · 2021: 92 · 2020: 54
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA207935, P01CA114046, R01CA174746, R01CA232256, P30CA010815, P30CA006973)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- tumor microenvironment, aging, tumor progression, extracellular matrix, secreted factors, cancer therapy response, tumour metastasis, preclinical mouse models
- MeSH terms
- Aging, Animals, Cell Transformation, Neoplastic, Combined Modality Therapy, Extracellular Matrix, Humans, Neoplasms, Treatment Outcome, Stromal Cells, Disease Progression, Tumor Microenvironment
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