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Cited by 1,262Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisCancer Immunotherapy and Biomarkers

The updated landscape of tumor microenvironment and drug repurposing

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Jin, Ming-Zhu, Jin, Wei-Lin·2020·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-020-00280-xPMC PMC7447642
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Abstract

Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

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  • The interplay between the gut microbiome and the tumor microenvironment constitutes a critical regulatory axis that modulates tumor initiation, growth, metastatic dissemination, and responsiveness to treatment.

    “Consequently, the interplay between the gut microbiome and the TME constitutes a critical regulatory axis that modulates tumor initiation, growth, metastatic dissemination, and responsiveness to treatment [11,43,45–47]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [47]

    The Discussion and outlook section says the gut microbiome can interact with gastrointestinal cancers and that microbiomes can influence carcinogenesis and therapies, while possibly contributing to metastasis. It does not specifically establish an effect on tumor growth, and it presents the role in metastasis and the microbiome–TME relationship as emerging and still poorly understood rather than as an established critical regulatory axis. Page numbers were not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The tumor microenvironment supports the survival and migration of cancer cells throughout the organism in response to internal or external stimuli, including treatments.

    “The TME supports the survival and migration of cancer cells throughout the organism in response to internal or external stimuli, including treatments.248”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [248]

  • 3D tumor spheroids are microsized cancer cell aggregates formed by 3D cell culture in vitro, categorized as homotypic spheroids and heterotypic spheroids.

    “3D tumor spheroids are microsized cancer cell aggregates formed by 3D cell culture in vitro, which can be categorized as homotypic spheroids (monoculture) and heterotypic spheroids (coculture of tumor cells and stromal cells).[ 43 ]”

    From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [43]

    The Metabolism microenvironment section mentions breast cancer cell spheroids in a comparison with monolayers, but does not define how spheroids are formed or classify them. Searches for “homotypic,” “heterotypic,” “monoculture,” and “coculture” found no passage addressing the claimed categories. No page number is available in our copy. (LLM, conf=0.73)

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Sorted by citations

Authors
Jin, M.-Z., & Jin, W.-L.
Affiliations
Shanghai Jiao Tong University (CN)
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2020-08-25
Volume
5
Issue
1
Pages
166-166
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-020-00280-x
PMC
PMC7447642
OpenAlex
W3080773873
Cited by
1,262
References
30
Citations by year
2026: 147 · 2025: 288 · 2024: 276 · 2023: 232 · 2022: 194 · 2021: 116 · 2020: 8
FWCI
14.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
12th Undergraduate Training Program for Innova- tion of Shanghai Jiao Tong University School of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
tumor microenvironment, drug repurposing, hypoxic niche, tumor immune microenvironment, aspirin, celecoxib, beta-blockers, metformin, statins, combination therapy, anticancer activity
MeSH terms
Humans, Metformin, Neoplasms, Drug Repositioning, Molecular Targeted Therapy, Tumor Microenvironment

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