Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 928, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2022.175087
Keywords
Tumor microenvironment; Cancer-associated fibroblasts; Tumor-associated macrophages; ECM; Metastasis; Immunotherapies
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The tumor microenvironment (TME) plays a crucial role in cancer metastasis and drug resistance. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) regulate angiogenesis, tumor metastasis, and drug resistance by manipulating the composition and organization of extracellular matrix (ECM). Targeting TAMs and CAFs is essential for enhancing the effectiveness of anti-cancer agents.
The tumor microenvironment (TME) and its components have recently attracted tremendous attention in cancer treatment strategies, as alongside the genetic and epigenetic alterations in tumor cells, TME could also provide a fertile background for malignant cells to survive and proliferate. Interestingly, TME plays a vital role in the mediation of cancer metastasis and drug resistance even against immunotherapeutic agents. Among different cells that are presenting in TME, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) have shown to have significant value in the regulation of angiogenesis, tumor metastasis, and drug-resistance through manipulating the composition as well as the organization of extracellular matrix (ECM). Evidence has shown that the presence of both TAMs and CAFs in TME is associated with poor prognosis and failure of chemotherapeutic agents. It seems that these cells together with ECM form a shield around tumor cells to protect them from the toxic agents and even the adaptive arm of the immune system, which is responsible for tumor surveillance. Given this, targeting TAMs and CAFs seems to be an essential approach to potentiate the cytotoxic effects of anti-cancer agents, either conventional chemotherapeutic drugs or immunotherapies. In the present review, we aimed to take a deep look at the mechanobiology of CAFs and TAMs in tumor progression and to discuss the available therapeutic approaches for harnessing these cells in TME.
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