期刊
FRONTIERS IN ONCOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.702642
关键词
cancer stem cells; tumor microenvironment; anticancer drugs; chemoresistance; targeted therapy
类别
资金
- AIRC [21492]
- AIRC IG [21445]
- PRIN [2017WNKSLR]
Despite advances in cancer patient management and targeted therapies, systemic chemotherapy remains the first-line treatment for many cancer types. Resistance to chemotherapeutic regimens is attributed to a subpopulation of cancer cells known as cancer stem cells (CSCs) within the tumor mass. Tumor microenvironment (TME) components such as adipocytes, cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells contribute to CSC chemoresistance through the release of growth factors and cytokines.
Despite the recent advances in cancer patient management and in the development of targeted therapies, systemic chemotherapy is currently used as a first-line treatment for many cancer types. After an initial partial response, patients become refractory to standard therapy fostering rapid tumor progression. Compelling evidence highlights that the resistance to chemotherapeutic regimens is a peculiarity of a subpopulation of cancer cells within tumor mass, known as cancer stem cells (CSCs). This cellular compartment is endowed with tumor-initiating and metastasis formation capabilities. CSC chemoresistance is sustained by a plethora of grow factors and cytokines released by neighboring tumor microenvironment (TME), which is mainly composed by adipocytes, cancer-associated fibroblasts (CAFs), immune and endothelial cells. TME strengthens CSC refractoriness to standard and targeted therapies by enhancing survival signaling pathways, DNA repair machinery, expression of drug efflux transporters and antiapoptotic proteins. In the last years many efforts have been made to understand CSC-TME crosstalk and develop therapeutic strategy halting this interplay. Here, we report the combinatorial approaches, which perturb the interaction network between CSCs and the different component of TME.
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