Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments

Cancers, Journal Year: 2022, Volume and Issue: 14(10), P. 2408 - 2408

Published: May 13, 2022

The importance of defining new molecules to fight cancer is significant interest the scientific community. In particular, it has been shown that stem cells (CSCs) are a small subpopulation within tumors with capabilities self-renewal, differentiation, and tumorigenicity; on other side, circulating tumor (CTCs) seem split away from primary appear in circulatory system as singular units or clusters. It becoming more important discover biomarkers related these populations combination define network among them microenvironment. cancer-associated fibroblasts (CAFs) key component microenvironment different functions, including matrix deposition remodeling, extensive reciprocal signaling interactions crosstalk immunity. settings markers definition molecular connections may present avenues, not only for fighting but also tailored therapies.

Language: Английский

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Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Stem Cell Reviews and Reports, Journal Year: 2022, Volume and Issue: 18(7), P. 2209 - 2233

Published: July 25, 2022

The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting progression metastasis. As result their preponderant involvement growth maintenance through several microsystemic alterations, including hypoxia, oxidative stress, acidosis, TMEs make for ideal targets both diagnostic therapeutic ventures. Correspondingly, methodologies target have been investigated this past decade as stratagems significant potential genre focused treatment. Within targeted oncotherapy, nanomedical derivates-nanocarriers (NCs) especially-have emerged present notable prospects enhancing targeting specificity. Yet, one major issue application NCs microenvironmental directed therapy is are too broad spectrum possibilities these carriers be effectively employed. However, stem cells (CSCs) might portend solution above conundrum: aside from being quite heavily invested tumorigenesis resistance, CSCs also show self-renewal fluid clonogenic properties often define specific TME niches. Further scrutiny relationship between points towards mechanisms underly tumoral characteristics metastasis, malignancy, even resistance. This review summarizes recent advances NC-enabled more holistic strikes against discusses current challenges hinder clinical strategies well avenues can further CSC-targeting initiatives. Central regulation cellular components within TME.

Language: Английский

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The complex network of transcription factors, immune checkpoint inhibitors and stemness features in colorectal cancer: A recent update

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 89, P. 1 - 17

Published: Jan. 6, 2023

Cancer immunity is regulated by several mechanisms that include co-stimulatory and/or co-inhibitory molecules known as immune checkpoints expressed the cells. In colorectal cancer (CRC), CTLA-4, LAG3, TIM-3 and PD-1 are major involved in tumor development progression. On other hand, deregulation of transcription factors stem cells activity plays a role drug resistance spread metastatic disease CRC. this review, we describe how modulation such affects response CRC to therapies. We also focus on metastasis chemoresistance discuss both preclinical clinical approaches for targeting prevent their tumorigenic effect. Finally, provide an update applications checkpoint inhibitors regulatory effects expression inhibitory with specific PD-L1 molecules.

Language: Английский

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The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Cells, Journal Year: 2023, Volume and Issue: 12(16), P. 2083 - 2083

Published: Aug. 17, 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading malignancy worldwide, with a poor prognosis limited treatment options. Molecularly targeted therapies for HNSCC are still lacking. However, recent reports provide novel insights about many molecular alterations in that may be useful future therapies. Therefore, it necessary to identify new biomarkers better prediction of disease promising targets personalized therapy. The response therapy attributed small population tumor cells called cancer stem (CSCs). Growing evidence indicates Hedgehog (HH) signaling pathway plays crucial role development maintenance head tissues. HH normally involved embryogenesis, renewal, tissue regeneration. abnormal activation also associated carcinogenesis CSC regulation. Overactivation was observed several tumors, including basal carcinoma, successfully treated inhibitors. clinical studies pathways rare. In this review, we summarize current knowledge advances regarding discuss its possible implications

Language: Английский

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SF1: A Standardised Fraction of Clinacanthus nutans That Inhibits the Stemness Properties of Cancer Stem-Like Cells Derived from Cervical Cancer

Sains Malaysiana, Journal Year: 2024, Volume and Issue: 53(3), P. 667 - 679

Published: March 20, 2024

Cancer stem cells (CSCs) are a small population of tumour that responsible for initiation, metastases, recurrence, and resistance to conventional therapy. Hence, targeting CSCs is crucial in the fight against cancer. SF1, standardised fraction from Clinacanthus nutans leaf extract, has been reported exhibit potent selective antineoplastic effects cervical cancer cells. In this study, potential SF1 inhibit stemness stem-like evaluated. extraction was carried out using dry column vacuum chromatography technique. SiHa cell lines were cultured as spheres CSC-conditioned medium (cervospheres), IC50 cervospheres determined OZBlue Cell Viability Kit. The on cervosphere’s markers, including CD49f, CK17, SOX2, OCT4, NANOG, assessed flow cytometry assay. Self-renewal inhibition anti-tumorigenesis evaluated sphere formation assay xenograft mouse model. present study shows treatment at an 17.07 µg/mL inhibited proliferation, self-renewal, tumorigenic capacity vitro vivo. A decrease expressions OCT4 indicated SF1’s inhibitory also associated with suppression markers. These results suggest possesses antitumor effect may be regarded promising approach development targeted anticancer agents

Language: Английский

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Small extracellular vesicles loaded with carboplatin effectively enhance the cytotoxicity of drug-resistant cells from Y79 cells-in vitro

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116403 - 116403

Published: March 15, 2024

Drug resistance (DR) is one of the challenges in treating retinoblastoma (Rb) that warrants novel approaches. With emerging evidence on role small extracellular vesicles (sEVs) as a drug-delivery carrier system, this study, we derived drug-resistant clones Y79 cells and evaluated efficacy sEVs-loaded with carboplatin (sEVs-CPT) to reverse chemoresistance. Drug-resistant (DR-Y79) were systematically developed through sequential exposure (CPT), showcasing sixfold increase inhibitory concentration when compared parental (IC50: 41.4 µg/mL 6.2 µg/mL) (P<0.0001). These DR-Y79 show higher expression ABCG2 DR genes than The sEVs isolated from conditioned media using ultracentrifugation (UC) characterized. Further, loaded CPT achieved encapsulation efficiency at hour, drug release sEVs-CPT was highest ∼80% pH 5.0. cytotoxicity 3.5 vs µg/mL; 23.1 41.2 (p<0.0001). This study demonstrates generates cells, which could serve an appropriate model evaluate drugs. highly effective enhancing appear hold promise complimentary delivery system.

Language: Английский

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Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 382 - 382

Published: Jan. 24, 2025

Cancer stem cells (CSCs) play a central role in tumor progression, recurrence, and resistance to conventional therapies, making them critical focus oncology research. This review provides comprehensive analysis of CSC biology, emphasizing their self-renewal, differentiation, dynamic interactions with the microenvironment (TME). Key signaling pathways, including Wnt, Notch, Hedgehog, are discussed detail highlight potential as therapeutic targets. Current methodologies for isolating CSCs critically examined, addressing advantages limitations advancing precision medicine. Emerging technologies, such CRISPR/Cas9 single-cell sequencing, explored transformative unraveling heterogeneity informing strategies. The also underscores pivotal TME supporting survival, promoting metastasis, contributing resistance. Challenges arising from CSC-driven dormancy analyzed, along strategies mitigate these barriers, novel therapeutics targeted approaches. Ethical considerations integration artificial intelligence designing CSC-specific therapies essential elements future manuscript advocates multi-disciplinary approach that combines innovative advanced therapeutics, collaborative research address complexities CSCs. By bridging existing gaps knowledge fostering advancements personalized medicine, this aims guide development more effective cancer treatment strategies, ultimately improving patient outcomes.

Language: Английский

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An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer

Future Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: Feb. 12, 2025

Triple-negative breast cancer (TNBC) presents a formidable global health challenge, marked by its aggressive behavior and significant treatment resistance. This subtype, devoid of estrogen, progesterone, HER2 receptors, largely relies on stem cells (BCSCs) for progression, metastasis, recurrence. BCSCs, characterized their self-renewal capacity resistance to conventional therapies, exploit key surface markers critical signaling pathways like Wnt, Hedgehog, Notch, TGF-β, PI3K/AKT/mTOR Hippo-YAP/TAZ thrive. Their adaptability is underscored mechanisms including drug efflux enhanced DNA repair, contributing poor prognosis high recurrence rates. The tumor microenvironment (TME) further facilitates BCSC survival through complex interactions with stromal immune cells. Emerging therapeutic strategies targeting BCSCs - ranging from immunotherapy nanoparticle-based delivery systems gene-editing technologies aim disrupt these resistant Additionally, innovative approaches focusing exosome-mediated metabolic reprogramming show promise in overcoming chemoresistance. By elucidating the distinct characteristics role TNBC, researchers are paving way novel treatments that may effectively eradicate resilient cells, mitigate ultimately improve patient outcomes. review highlights urgent need targeted address unique biology pursuit more effective interventions TNBC.

Language: Английский

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Antitumor effects of BPCO on liver cancer cells

Journal of Asian Natural Products Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Feb. 22, 2025

Esculetin is a coumarin compound with anticancer, antioxidant, and anti-inflammatory activities. In this study, we synthesized an esculetin derivative, 6,7-bis(Pentyloxy)-2H-Chromen-2-One (BPCO), through etherification. BPCO inhibited the proliferation of HepG2 cells in dose- time-dependent manner. It also cell migration, promoted apoptosis, caused cycle arrest at G1 phase. Additionally, downregulated expression levels Bcl-2 Bcl-XL upregulated Bax Bak. This study shows that inhibits hepatocellular carcinoma induces providing basis for further as antitumor agent.

Language: Английский

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A Truncated Mutation of TP53 Promotes Chemoresistance in Tongue Squamous Cell Carcinoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2353 - 2353

Published: March 6, 2025

Tongue squamous cell carcinoma (TSCC), a subtype of head and neck carcinoma, is characterized by frequent chemoresistance. Genetic mutations commonly observed in TSCC play critical role malignant progression; thus, elucidating their functional significance essential for developing effective treatment strategies. To more accurately investigate the relationship between chemoresistance, we established low-passage cells, CTSC-1, obtained from chemoresistant patient, CTSC-2, treatment-naïve patient. Sanger sequencing revealed specific TP53 mutation (Q331*) leading to loss tetramerization C-terminal regulatory domains. Notably, CTSC-1 cells harboring TP53-Q331* CTSC-2 with knockout that have been engineered ectopically express exhibit enhanced chemoresistance increased cancer stem cell-like properties. Mechanistically, upregulates expression inhibitor DNA binding 2 (ID2), which crucial maintaining stemness cells. Subsequently, ID2 activates nucleotide excision repair (NER) pathway-related genes ERCC4 ERCC8, thereby enhancing TSCC. In conclusion, our study demonstrates enhances through an ID2-mediated NER pathway, providing potential prognostic marker therapeutic target chemotherapy resistance.

Language: Английский

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