Version 1
: Received: 27 October 2022 / Approved: 28 October 2022 / Online: 28 October 2022 (09:57:34 CEST)
How to cite:
Dzobo, K.; Senthebane, D.; Dandara, C. The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited. Preprints2022, 2022100450. https://doi.org/10.20944/preprints202210.0450.v1
Dzobo, K.; Senthebane, D.; Dandara, C. The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited. Preprints 2022, 2022100450. https://doi.org/10.20944/preprints202210.0450.v1
Dzobo, K.; Senthebane, D.; Dandara, C. The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited. Preprints2022, 2022100450. https://doi.org/10.20944/preprints202210.0450.v1
APA Style
Dzobo, K., Senthebane, D., & Dandara, C. (2022). The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited. Preprints. https://doi.org/10.20944/preprints202210.0450.v1
Chicago/Turabian Style
Dzobo, K., Dimakatso Senthebane and Collet Dandara. 2022 "The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited" Preprints. https://doi.org/10.20944/preprints202210.0450.v1
Abstract
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis and highlight various ways through which tumor cells reprogram normal cells including into phenotypes that are pro-tumorigenic including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to formation of new vascular networks in order to actively promote and sustain tumor growth via supply of oxygen and nutrients whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to targeting of tumor cells. Re-programming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centred therapies under investigations.
Keywords
Tumor microenvironment; stromal cells; immune cells; ECM; cancer hallmarks; hypoxia; exosomes; drug resistance; targeted therapy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
