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The Tumor Microenvironment: Impact on Tumor Growth, Metastasis, and Therapeutic Resistance: A Systematic Review
1Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
Introduction:
This systematic review assesses the role of the tumor microenvironment (TME) in cancer progression and therapy resistance by defining drug-microenvironment interactions and determining the molecular determinants in the TME that could help improve the efficacy of administered treatments and alleviate existing adverse effects.
Methods:
This systematic review follows the PRISMA protocol and the PICOS selection framework to retrieve studies from PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. Only original human-related research published in English between 2008 and 2023 was used to explore the reciprocal relation between tumor cells and TME components. The ROBINS-I tool assessed the risk of bias.
Results:
Out of 258 articles initially identified, 15 met the inclusion criteria for this review. The results showed that TMEs significantly influence treatment outcomes in cancer progression, metastasis, and drug resistance. Focusing on TMEs like CAFs, immune cells, and ECM enhances drug efficacy. The study highlighted potential strategies to improve drug delivery, suppress metastatic processes, and restore immune function, ultimately leading to better outcomes for cancer patients.
Discussion:
Original evidence suggests that Cancer-Associated Fibroblasts (CAFs), immune cells, and Extracellular Matrix (ECM) contribute to therapeutic resistance and metastasis within the TME. They also promote metastasis by inducing Epithelial- Mesenchymal Transition (EMT) and affecting Cancer Stem Cell (CSC) populations. Moreover, the immunosuppressive TME consists of regulatory T cells and myeloidderived suppressor cells that allow tumors to evade the immune system, a concern for immunotherapy.
Conclusion:
The TME plays a vital role in cancer development, metastasis formation, and therapy failure. The perspectives for innovative ECM-modulating treatments and interventions targeting the direct interactions between TME and cancer cells can be revolutionary and suggest better outcomes for treatment-naïve and refractory cancers. Future research should use these results as inputs to apply clinical and therapy studies to enhance cancer management outcomes.
Insights
The tumor microenvironment (TME) significantly impacts cancer progression and treatment resistance. Targeting components like cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) can enhance therapy efficacy and improve patient outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- The tumor microenvironment (TME) is crucial in cancer progression and therapy resistance.
- Understanding drug-microenvironment interactions is key to improving cancer treatments.
- Identifying molecular determinants within the TME can enhance treatment efficacy and reduce adverse effects.
Purpose of the Study:
- To systematically review the role of the TME in cancer progression and therapy resistance.
- To define drug-microenvironment interactions and identify molecular determinants.
- To explore strategies for improving cancer treatment efficacy by targeting the TME.
Main Methods:
- Systematic review following PRISMA protocol and PICOS framework.
- Literature search of PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library.
- Inclusion of original human research published in English (2008-2023); risk of bias assessed using ROBINS-I.
Main Results:
- 15 studies met inclusion criteria from 258 initial articles.
- TMEs significantly influence cancer progression, metastasis, and drug resistance.
- Targeting CAFs, immune cells, and ECM enhances drug efficacy and improves outcomes.
Conclusions:
- CAFs, immune cells, and ECM drive therapeutic resistance and metastasis.
- The TME promotes metastasis via EMT and affects CSC populations.
- Targeting TME interactions offers revolutionary potential for cancer treatment.
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