Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies

Czerwonka, Arkadiusz; Kałafut, Joanna; Nees, Matthias

doi:10.3390/cancers15184563

Cited by 5 publications

(3 citation statements)

References 230 publications

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“…These studies have shed light on previously unexplored areas of NOTCH signaling, presenting exciting opportunities for further research. To develop targeted therapies successfully, it is imperative to obtain a comprehensive understanding of NOTCH signaling, necessitating ongoing efforts and exploration in this field 85 .…”

Section: The Structure Of Notch Signallingmentioning

confidence: 99%

Navigating breast cancer complexity: Deciphering the cross talk of Wnt/β catenin and Notch pathways in development and diseases

Rasool,

Bhat,

Khurshid

et al. 2024

Preprint

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This study investigates miRNA impact on lung, colorectal, and epithelial cancers, emphasizing Wnt3’s role in breast tumor growth through WNT signaling and its influence on mammary stem cells. WNT pathway inactivation induces drug-insensitive, quiescent states in breast cancer stem cells, resulting in resistance to multiple drugs. Tamoxifen-resistant breast carcinoma cells activate both canonical and noncanonical WNT signaling, with Wnt3a enhancing tamoxifen resistance in ER+ carcinoma cells. The study also explores breast cancer immunotherapy, highlighting immune checkpoint blockade targeting PD-1/PD-L1 and CTLA-4 as promising avenues. Additionally, the study explores the NOTCH signaling pathways impact on cancer proliferation, apoptosis, invasion and metastasis. Elevated NOTCH receptor and ligand expression particularly in aggressive triple negative breast cancer correlate with poorer treatment outcome, serving as a predictor for adverse results in breast tumors. The review discusses the relevance of Notch signaling in therapy resistance and breast cancer recurrence. The article encapsulates therapeutic advancements targeting the Notch signaling pathway, weighing merits and demerits in the context of breast cancer treatment. Our study provides a comprehensive understanding of the complex interactions within the WNT and Notch signaling pathways in breast cancer, shedding light on potential therapeutic targets and strategies for personalized treatment. This research significantly contributes to the current body of knowledge, offering promise for improved outcomes in breast cancer patients. The findings underscore the importance of WNT and Notch signaling modulation in developing effective therapeutic interventions for breast cancer.

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Section: The Structure Of Notch Signallingmentioning

confidence: 99%

Navigating breast cancer complexity: Deciphering the cross talk of Wnt/β catenin and Notch pathways in development and diseases

Rasool,

Bhat,

Khurshid

et al. 2024

Preprint

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show abstract

“…The Notch signaling pathway is crucial for diverse biological processes, facilitating cell–cell interaction and regulating cell proliferation, differentiation, and inflammatory responses. 78 , 79 , 80 In radiation‐induced brain injury, Notch signaling pathway plays a significant role in neuroinflammation, neuronal damage, and vascular remodeling. Microglia play a pivotal role in this process, with their activation being influenced by Notch signaling.…”

Section: Signal Pathways Of Microglia In Radiation‐induced Brain Injurymentioning

confidence: 99%

Microglia in radiation‐induced brain injury: Cellular and molecular mechanisms and therapeutic potential

Wang,

Tian,

Liu

et al. 2024

CNS Neurosci Ther

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BackgroundRadiation‐induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation‐induced brain injury.MethodsThis article critically examines recent developments in understanding the role of microglia activation in radiation‐induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition.ResultsPost‐irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation‐induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation‐induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation‐induced brain injury.ConclusionsThe intricate microenvironment and molecular mechanisms associated with radiation‐induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.

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“…While gastrointestinal side effects have been reported with nonspecific NOTCH inhibitor drugs administration in mice [ 48 ], no clinical side effects or pathologic changes in organs other than the lungs with anti-NOTCH3 Ab 28042 treatment were observed [ 14 ].…”

Section: Monoclonal Antibody That Blocks Jag-1/notch3 Binding Inhibit...mentioning

confidence: 99%

NOTCH3 and Pulmonary Arterial Hypertension

Winicki,

Puerta,

Besse

et al. 2024

IJMS

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NOTCH3 receptor signaling has been linked to the regulation of smooth muscle cell proliferation and the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (World Health Organization Group 1 idiopathic disease: PAH) is a fatal disease characterized clinically by elevated pulmonary vascular resistance caused by extensive vascular smooth muscle cell proliferation, perivascular inflammation, and asymmetric neointimal hyperplasia in precapillary pulmonary arteries. In this review, a detailed overview of the specific role of NOTCH3 signaling in PAH, including its mechanisms of activation by a select ligand, downstream signaling effectors, and physiologic effects within the pulmonary vascular tree, is provided. Animal models showing the importance of the NOTCH3 pathway in clinical PAH will be discussed. New drugs and biologics that inhibit NOTCH3 signaling and reverse this deadly disease are highlighted.

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Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies

Cited by 5 publications

References 230 publications

Navigating breast cancer complexity: Deciphering the cross talk of Wnt/β catenin and Notch pathways in development and diseases

Navigating breast cancer complexity: Deciphering the cross talk of Wnt/β catenin and Notch pathways in development and diseases

Microglia in radiation‐induced brain injury: Cellular and molecular mechanisms and therapeutic potential

NOTCH3 and Pulmonary Arterial Hypertension

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