γ-Secretase inhibitor–resistant glioblastoma stem cells require RBPJ to propagate

Fan, Xing

doi:10.1172/jci88619

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…In another approach, γ secretase inhibitors were found resistant for brain tumor initiating cells with high level of RBPJ. Targeting CDK9 or c-MYC, an upstream regulator of RBPJ, with small molecules also decreased BTIC propagation, and prolonged survival in mice bearing orthotopic GBM xenografts [41].…”

Section: Cdk6 Inhibitorsmentioning

confidence: 96%

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

Parveen¹,

Ashfaq²,

Shahid³

et al. 2021

J Biomed Res Environ Sci

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Within a tumor, Cancer Stem Cells (CSCs) exists and own similar characteristics of a normal stem cell thus contributing towards aggressiveness of cancer by playing crucial role in tumor recurrence and metastasis capability. Various studies have been conducted to therapeutically target CSCs. One of the approaches include is to inhibit cell cycle progression in CSCs. Within last two decades cell cycle and role of various components in its regulation is firmly established. Cell cycle is regulated by Cyclin Dependent Kinases (CDK) bound to cyclin. CDK activity can be blocked by Cyclin-Dependent Kinase Inhibitors (CKIs) which can either bind cyclin/CDK complex or CDK alone and thus stops cell cycle. In this review various studies are discussed that have investigated the therapeutic role of CKIs in eradicating CSCs by inhibiting cell cycle. Overall, the analysis suggests that CKIs could be a potential therapeutic option in controlling CSCs populating in a tumor.

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Section: Cdk6 Inhibitorsmentioning

confidence: 96%

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

Parveen¹,

Ashfaq²,

Shahid³

et al. 2021

J Biomed Res Environ Sci

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“…Активация сигнального пути Notch служит также триггером для прогрессии опухоли в более агрессивный фенотип. Исследования in vitro и in vivo показали, что блокирование сигнального пути Notch ингибиторами γ-секретазы приводило к снижению роста опухоли, индукции апоптоза, даун-регуляции ММП-2 и 9 и, как результат, снижало метастазирование [41,42]. При блокаде сигнального пути Notch с помощью ингибиторов γ-секретазы в опухолевых клетках рака мозга было обнаружено снижение доли CD133-положительных клеток (СКО) в 5 раз.…”

Section: обзоры литературыunclassified

“…При блокаде сигнального пути Notch с помощью ингибиторов γ-секретазы в опухолевых клетках рака мозга было обнаружено снижение доли CD133-положительных клеток (СКО) в 5 раз. Уровень апоптоза был также выше -почти в 10 раз [42]. Продолжаются клинические испытания с антителами к DLL-4 и Notch-1 [43].…”

Section: обзоры литературыunclassified

Therapies Targeting Cancer Stem Cells of the Tumor: The One and Only Hope

Vartanyan¹,

Барышников²

2016

Rossijskij bioterapevtičeskij žurnal

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The basic problem in cancer treatment remains the identification of cells responsible for maintaining the whole population of cells in a tumor. For decades it has been considered that all transformed cells within a tumor have carcinogenic potential with unlimited proliferation capacity and metastases formation. At present, the concept of cancer stem cell was introduced indicating that tumor evolves from a small population of long-live and slow proliferating cells. These cells have the capacity to initiate the tumor formation in immunodeficient animals. Among their properties, resistance to standard oncology treatments leads to treatment failure and cancer recurrence. The management and eradication of different types cancer is completely depended on removal of this cell population. Current review presents basic information about cancer stem cell, particularly, the initiation of tumor, the peculiar properties of cancer stem cell, the role of cancer stem cell in metastasis formation and discusses therapeutic strategies targeted cancer stem cell.

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“…Basic and clinical trials have reported the antitumor activity of GSIs, although these studies have been conducted on a small sample size of solid tumors [ 29 ]. Apart from inhibiting cell proliferation and inducing cell apoptosis by inhibiting the crack of Notch-3, GSI is associated with increasing the sensitivity of NSCLC cell lines to platinum chemotherapy, supporting the concept that GSI can be useful in chemotherapy treatment and recurrent cancer [ 30 ]. Thus, it is necessary to explore the molecular mechanisms in order to obtain greater insight into the role of GSI in the treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 96%

Synergistic Effect of Notch-3-Specific Inhibition and Paclitaxel in Non-Small Cell Lung Cancer (NSCLC) Cells Via Activation of The Intrinsic Apoptosis Pathway

Jiao

et al. 2017

Med Sci Monit

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BackgroundLung cancers are resistant to conventional chemotherapeutic interventions such as paclitaxel. Notch signaling is crucial in the chemoresistance of lung cancer cells. The Notch inhibitor gamma-secretase inhibitor (GSI) inhibits the Notch signaling pathway.Material/MethodsHere, we evaluated how Notch-3 inhibition by GSI can enhance the sensitivity of lung cancer cells to paclitaxel. To study how Notch-3-specific inhibition affects non-small cell lung cancer (NSCLC), we compared the cell viability, apoptosis, and colony formation of A549 and H1299 cells treated with Notch-3 siRNA and GSI.ResultsThe expression levels of Notch-3 or Notch intracellular domain 3 (NICD3) and apoptosis-related proteins were measured and compared between different groups. Notch-3 was significantly overexpressed in both cell lines, and Notch-3 expression was elevated after paclitaxel treatment, indicating activation of the Notch signaling pathway. Inhibition of the Notch signaling pathway by GSI and Notch-3 siRNA reduced cell proliferation and induced apoptosis in A549 and H1299 cells, thereby boosting sensitivity of the cell lines to paclitaxel. Concomitant treatment with paclitaxel and GSI or siRNA downregulated Bcl-2 expression and upregulated Bax expression levels.ConclusionsThese results indicate a synergistic effect of Notch-3-specific inhibition and paclitaxel through alteration of the intrinsic apoptosis pathway, which was involved in Notch-3-induced chemoresistance in NSCLC cells, and GSI inhibited Notch-3-induced chemoresistance in a concentration-dependent manner. This approach that combines Notch-3-specific inhibition and paclitaxel would be likely to apply in NSCLC.

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γ-Secretase inhibitor–resistant glioblastoma stem cells require RBPJ to propagate

Abstract: C o m m e n t a r y 2 4 1 5

Cited by 7 publications

References 43 publications

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

Therapies Targeting Cancer Stem Cells of the Tumor: The One and Only Hope

Synergistic Effect of Notch-3-Specific Inhibition and Paclitaxel in Non-Small Cell Lung Cancer (NSCLC) Cells Via Activation of The Intrinsic Apoptosis Pathway

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