Abstract
Soft tissue sarcomas (STS) are a rare group of mesenchymal solid tumors with heterogeneous genetic profiles and clinical features. Systemic chemotherapy is the backbone treatment for advanced STS; however, STS frequently acquire resistance to standard therapies, which highlights the need to improve treatments and identify novel therapeutic targets. Increases in the knowledge of the molecular pathways that drive sarcomas have brought to light different molecular alterations that cause tumor initiation and progression. These findings have triggered a breakthrough of targeted therapies that are being assessed in clinical trials. Cancer stem cells (CSCs) exhibit mesenchymal stem cell (MSC) features and represent a subpopulation of tumor cells that play an important role in tumor progression, chemotherapy resistance, recurrence and metastasis. In fact, CSCs phenotypes have been identified in sarcomas, allied to drug resistance and tumorigenesis. Herein, we will review the published evidence of CSCs in STS, discussing the molecular characteristic of CSCs, the commonly used isolation techniques and the new possibilities of targeting CSCs as a way to improve STS treatment and consequently patient outcome.
Highlights
Cancer stem cells (CSCs), known as tumor-initiating cells (TICs), are cancer cells that display distinctive features of normal stem cells and that have the ability to give origin to all cell types of a particular cancer sample
The combination of liposomal doxorubicin and temsirolimus has led to a PFS three times longer, compared to the results obtained with a mTOR inhibitor in monotherapy [89], and at least two times longer compared with liposomal doxorubicin alone or in combination with other conventional chemotherapy agents [93,94]
From a mechanistic point-of-view, ALKATI was reported to interact with c-Myc, increasing its binding to the ABCG2 promoter and inducing stem cell-like features in Soft tissue sarcomas (STS) [104]
Summary
Cancer stem cells (CSCs), known as tumor-initiating cells (TICs), are cancer cells that display distinctive features of normal stem cells and that have the ability to give origin to all cell types of a particular cancer sample. Several surface markers that over time have been described to be expressed by cells showing distinctive features of CSCs, such as high proliferative rate, high clonogenicity and tumorigenicity, have been used with the purpose of identifying them among the heterogeneous cell populations of STS, and as outcome predictors. Their role and use for detection of CSCs in STS remains controversial, due to the fact that many CSC markers could define normal MSCs [4].
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