DLL3 regulates Notch signaling in small cell lung cancer

Kim, Jun W.; Ko, Julie; Sage, Julien

doi:10.1016/j.isci.2022.105603

Cited by 13 publications

(8 citation statements)

References 62 publications

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“…Additional clinical trials were motivated by positive results. The optimistic results of rovelizumab tsarina (Rova-T) were originally published by Charles M. Rudin et al in 2017; 11 of 60 attainable SCLC or LCNEC patients had confirmed objective responses, and the objective response rate (ORR) was comparatively greater in patients with strong DLL3 expression 168,169 . Despite a significant proportion of the study population (38% of 74 individuals) experiencing serious drugrelated adverse events, 579 participants were able to manage these adverse effects effectively.…”

Section: Dll3mentioning

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: Dll3mentioning

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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“… 148 Functionally, DLL3 acts as a regulator of cell-cell interactions in the neuroendocrine state of SCLC. 149 Numerous preclinical and clinical studies targeting DLL3 are underway, defining it as a promising treatment strategy for SCLC. 150 , 151 …”

Section: The Notch Signaling Pathway and Cancermentioning

confidence: 99%

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Shi,

Xue,

Zeng

et al. 2024

Sig Transduct Target Ther

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Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

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“…Due to the overexpression of Delta-like canonical Notch ligand 3 (DLL3) in SCLC, it is therefore considered a promising therapeutic vulnerability in SCLC [ 119 , 120 ]. In Tanaka’s study where a total of 63 patients with SCLC were immunohistochemically stained for DLL3, DLL3-positive tumors account for 83%, and DLL3-high tumors accounts for 32% [ 121 ].…”

Section: Developmental Pathwaysmentioning

confidence: 99%

Orchestrating smart therapeutics to achieve optimal treatment in small cell lung cancer: recent progress and future directions

Zhang

Wang

et al. 2023

J Transl Med

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Small cell lung cancer (SCLC) is a recalcitrant malignancy with elusive mechanism of pathogenesis and dismal prognosis. Over the past decades, platinum-based chemotherapy has been the backbone treatment for SCLC. However, subsequent chemoresistance after initial effectiveness urges researchers to explore novel therapeutic targets of SCLC. Recent years have witnessed significant improvements in targeted therapy in SCLC. New molecular candidates such as Ataxia telangiectasia and RAD3-related protein (ATR), WEE1, checkpoint kinase 1 (CHK1) and poly-ADP-ribose polymerase (PARP) have shown promising therapeutic utility in SCLC. While immune checkpoint inhibitor (ICI) has emerged as an indispensable treatment modality for SCLC, approaches to boost efficacy and reduce toxicity as well as selection of reliable biomarkers for ICI in SCLC have remained elusive and warrants our further investigation. Given the increasing importance of precision medicine in SCLC, optimal subtyping of SCLC using multi-omics have gradually applied into clinical practice, which may identify more drug targets and better tailor treatment strategies to each individual patient. The present review summarizes recent progress and future directions in SCLC. In addition to the emerging new therapeutics, we also focus on the establishment of predictive model for early detection of SCLC. More importantly, we also propose a multi-dimensional model in the prognosis of SCLC to ultimately attain the goal of accurate treatment of SCLC.

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DLL3 regulates Notch signaling in small cell lung cancer

Cited by 13 publications

References 62 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

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Orchestrating smart therapeutics to achieve optimal treatment in small cell lung cancer: recent progress and future directions

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