Abstract
Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs), a subset of cells within the tumor with the potential for self-renewal, differentiation and tumorigenicity, are thought to be the major cause of cancer therapy failure due to their considerable chemo- and radioresistance, resulting in tumor recurrence and eventually metastasis. CSCs are situated in a specialized microenvironment termed the niche, mainly composed of fibroblasts and endothelial, mesenchymal and immune cells, which also play pivotal roles in drug resistance. These neighboring cells promote the molecular signaling pathways required for CSC maintenance and survival and also trigger endogenous drug resistance in CSCs. In addition, tumor niche components such as the extracellular matrix also physically shelter CSCs from therapeutic agents. Interestingly, CSCs contribute directly to the niche in a bilateral feedback loop manner. Here, we review the recent advances in the study of CSCs, the niche and especially their collective contribution to resistance, since increasingly studies suggest that this interaction should be considered as a target for therapeutic strategies.
Highlights
Cancer is one of the most devastating diseases worldwide
Tumor-initiating cells or cancer stem cells, as they will be referred into this article, are a small subpopulation of cells within a tumor that retain the capacity for self-renewal and are able to differentiate into the heterogeneous lineages that comprise the tumor
cancer stem cells (CSCs) are localized in a specific microenvironment referred to as the niche, which is formed by a variety of cells that promote CSC survival and enhance their characteristics
Summary
Cancer is one of the most devastating diseases worldwide. In 2016, more than 1.5 million people were afflicted in the U.S Despite recent major advances in understanding the molecular and genetic basis of cancer, more than one third of afflicted people die each year [1]. Tumor-initiating cells or cancer stem cells, as they will be referred into this article, are a small subpopulation of cells within a tumor that retain the capacity for self-renewal and are able to differentiate into the heterogeneous lineages that comprise the tumor. They possess high tumorigenicity capacity and are thought to be highly resistant to radiation and chemotherapy, making them capable of repopulating a tumor after treatment [3]. An in-depth understanding of the biological characteristics of CSCs and in particular their role in drug resistance, is crucial for establishing novel tumor diagnostic and therapeutic strategies. We review the recent known mechanisms used by CSCs to overcome drug treatment, as well as the role of the niche in CSCs and drug resistance and examine their implications for novel therapeutic strategies
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