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Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

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Title: Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.
Authors: Mengistu, Bemrew Admassu, Demessie, Yitayew, Kinde, Mebrie Zemene, Getnet, Kalkidan, Bitew, Abebe Belete, Berrie, Kassahun, Sendeku, Wagaw, Berihun, Asnakew Mulaw, Abat, Anmaw Shite, Mebratu, Atsede Solomon, Feleke, Melaku Getahun, Yesist, Nesibu Tilahun, Ferede, Melkamu Molla, Fenta, Melkie Dagnaw
Source: Cancer Cell International; 10/28/2025, Vol. 25 Issue 1, p1-39, 39p
Subject Terms: CANCER stem cells, TUMOR microenvironment, CANCER treatment, DRUG resistance, STEM cells, CARCINOGENESIS, METASTASIS
Abstract: This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signaling pathways, including Wnt/β-catenin, Notch, and Hedgehog signaling cascades. The tumor microenvironment (TME) significantly influences CSC dynamics by providing a nurturing niche that enhances CSC survival, enables immune evasion, and contributes to resistance against therapies. Key components of the TME, such as cancer-associated fibroblasts and immune-modulating exosomes, play a crucial role in augmenting CSC plasticity and metastatic capabilities. Furthermore, the hypoxic environment prevalent within the TME enhances CSC stemness through both metabolic and epigenetic alterations. Despite the existence of promising CSC-targeted therapeutic strategies, including immunotherapy, small-molecule inhibitors, and combinatorial approaches, notable challenges persist. These obstacles include CSC plasticity and heterogeneity, as well as the potential for immune rejection of CSC-targeted therapies. Advancements in precision medicine, genomics, and novel therapeutic interventions instill hope for the improvement of CSC-targeted strategies. A comprehensive understanding of the fluid interactions between CSCs, standard stem cells, and the TME is vital for advancing personalized cancer treatments that enhance patient success and reduce recurrence rates. This review highlights the need for continued research to bridge existing knowledge gaps and facilitate the translation of foundational scientific discoveries into clinical practices. [ABSTRACT FROM AUTHOR]
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Database: Biomedical Index
Description
Abstract:This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signaling pathways, including Wnt/β-catenin, Notch, and Hedgehog signaling cascades. The tumor microenvironment (TME) significantly influences CSC dynamics by providing a nurturing niche that enhances CSC survival, enables immune evasion, and contributes to resistance against therapies. Key components of the TME, such as cancer-associated fibroblasts and immune-modulating exosomes, play a crucial role in augmenting CSC plasticity and metastatic capabilities. Furthermore, the hypoxic environment prevalent within the TME enhances CSC stemness through both metabolic and epigenetic alterations. Despite the existence of promising CSC-targeted therapeutic strategies, including immunotherapy, small-molecule inhibitors, and combinatorial approaches, notable challenges persist. These obstacles include CSC plasticity and heterogeneity, as well as the potential for immune rejection of CSC-targeted therapies. Advancements in precision medicine, genomics, and novel therapeutic interventions instill hope for the improvement of CSC-targeted strategies. A comprehensive understanding of the fluid interactions between CSCs, standard stem cells, and the TME is vital for advancing personalized cancer treatments that enhance patient success and reduce recurrence rates. This review highlights the need for continued research to bridge existing knowledge gaps and facilitate the translation of foundational scientific discoveries into clinical practices. [ABSTRACT FROM AUTHOR]
ISSN:14752867
DOI:10.1186/s12935-025-03981-x