Abstract
Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies.
Highlights
In 2018, the World Health Organization (WHO) asserted that cancer is responsible for the death of9.6 million people worldwide [1]
TGF-β binding to its receptors results in the activation of the SMAD proteins that translocate to the nucleus and activate target genes involved in epithelial-mesenchymal transition (EMT) such as SNAIL, bHLH and ZEB factors [124,125]
Progress has been made in developing cancer therapies that target cancer stem cells (CSCs), the specificity of the targeted antigens remains a challenge
Summary
In 2018, the World Health Organization (WHO) asserted that cancer is responsible for the death of. The data suggest that despite the availability of different drugs, their efficacy requires further improvement with a focus on cancer complexity In this intricate system, cancer stem cells play a crucial role, as they mediate chemoresistance and cancer recurrence. CSCs appear to be generated from mutations affecting adult stem cells that are at the source of organogenesis and tissue homeostasis [2,3,4] Debates about their origin persist, there is an urgent and continuous need to better understand the function of CSCs in cancer initiation and progression and, more importantly, develop CSC-specific targeting strategies. A major challenge in cancer therapy is associated with chemoresistance and recurrence following chemotherapy [2,39] In most cases, this resistance is associated with the presence, within tumours, of aggressive cancer cell populations that developed mechanisms of chemoresistance responsible for unsuccessful therapies and leading to decreased survival rates of treated cancer patients.
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