Cancer stem cells (CSC) are important to understand in order to develop solutions to treat tumor metastasis and resistance to therapy. CSCs are characterized by their ability to self-renew and differentiate into tumors, ultimately leading to therapeutic resistance. This chapter summarizes the various potential therapeutic approaches to control CSCs survival and proliferation based on preclinical and clinical study-based rationale. The proposed agents range from investigational, which are still in pre-clinical stage, already in early clinical investigational stage, or already approved for clinical use for other indications. The manuscript covers the agents targeting embryonic stem cell signaling, epigenetic control, cancer metabolism, and induction of epithelial-to-mesenchymal transition (EMT). The combination of therapeutic strategies to reduce bulk tumor populations and to target CSCs population may provide clinically meaningful tumor suppression. The development of new anti-CSC therapeutic agents and the complexity of potential molecular pathways controlling CSC survival are described in this review.
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