Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic cancer remains elusive. A major hurdle in treatment success is the ability of cancer cells, particularly cancer stem cells (CSCs), to resist therap...

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Bibliographic Details
Published in:Cancer cell international 2024-12, Vol.24 (1), p.406-38
Main Authors: Mengistu, Bemrew Admassu, Tsegaw, Tirunesh, Demessie, Yitayew, Getnet, Kalkidan, Bitew, Abebe Belete, Kinde, Mebrie Zemene, Beirhun, Asnakew Mulaw, Mebratu, Atsede Solomon, Mekasha, Yesuneh Tefera, Feleke, Melaku Getahun, Fenta, Melkie Dagnaw
Format: Article
Language:English
Subjects:
Cancer cells
Cancer stem cells
Drug resistance
Mammalian cancer stem cells
Review
Online Access:Get full text
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Summary:Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic cancer remains elusive. A major hurdle in treatment success is the ability of cancer cells, particularly cancer stem cells (CSCs), to resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, and repair, which drive tumor progression and chemotherapy resistance. The resilience of CSCs is linked to certain signaling pathways. Tumors with pathway-dependent CSCs often develop genetic resistance, whereas those with pathway-independent CSCs undergo epigenetic changes that affect gene regulation. CSCs can evade cytotoxic drugs, radiation, and apoptosis by increasing drug efflux transporter activity and activating survival mechanisms. Future research should prioritize the identification of new biomarkers and signaling molecules to better understand drug resistance. The use of cutting-edge approaches, such as bioinformatics, genomics, proteomics, and nanotechnology, offers potential solutions to this challenge. Key strategies include developing targeted therapies, employing nanocarriers for precise drug delivery, and focusing on CSC-targeted pathways such as the Wnt, Notch, and Hedgehog pathways. Additionally, investigating multitarget inhibitors, immunotherapy, and nanodrug delivery systems is critical for overcoming drug resistance in cancer cells.
ISSN:1475-2867
1475-2867
DOI:10.1186/s12935-024-03558-0