<scp>DLL</scp>3 regulates the migration and invasion of small cell lung cancer by modulating Snail

Furuta, Megumi; Kikuchi, Hajime; Shoji, Tetsuaki; Takashima, Yuta; Kikuchi, Eiki; Kikuchi, Junko; Kinoshita, Ichiro; Dosaka‐Akita, Hirotoshi; Sakakibara‐Konishi, Jun

doi:10.1111/cas.13997

Cited by 53 publications

(37 citation statements)

References 41 publications

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“…DLL3, an inhibitory ligand of the Notch signaling pathway, highly expressed on the surface of SCLC tumor cells, is correlated with tumor progression of SCLC [ [93] , [94] , [95] ]. Rova-T is known as a humanized monoclonal antibody directed against DLL3.…”

Section: Icis In Combination With Rovalpituzumab Tesirine (Rova-t)mentioning

confidence: 99%

Combination therapy: Future directions of immunotherapy in small cell lung cancer

Huang

Chen

Xing

et al. 2021

Translational Oncology

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Small cell lung cancer (SCLC), an aggressive and devastating malignancy, is characterized by rapid growth and early metastasis. Although most patients respond to first-line chemotherapy, the majority of patients rapidly relapse and have a relatively poor prognosis. Fortunately, immunotherapy, mainly including antibodies that target the cytotoxic T lymphocyte antigen-4 (CTLA-4), checkpoints programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) to block immune regulatory checkpoints on tumor cells, immune cells, fibroblasts cells and endothelial cells, has achieved the milestone in several solid tumors, such as melanoma and non-small-cell lung carcinomas (NSCLC). In recent years, immunotherapy has made progress in the treatment of patients with SCLC, while its response rate is relatively low to monotherapy. Interestingly, the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, preliminarily achieve greater therapeutic effects for treating SCLC. Combining different immunotherapy drugs may act synergistically because of the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of chemoradiotherapy in immunotherapy may augment antitumor immune responses because chemoradiotherapy can enhance tumor cell immunogenicity by rapidly inducing tumor lysis and releasing tumor antigens. In addition, since immunotherapy drugs and the molecular targets drugs act on different targets and cells, the combination of these drugs may achieve greater therapeutic effects in the treatment of SCLC. In this review, we focused on the completed and ongoing trials of the combination therapy for immunotherapy of SCLC to find out the rational combination strategies which may improve the outcomes for SCLC.

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Section: Icis In Combination With Rovalpituzumab Tesirine (Rova-t)mentioning

confidence: 99%

Combination therapy: Future directions of immunotherapy in small cell lung cancer

Huang

Chen

Xing

et al. 2021

Translational Oncology

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“…Of course, further investigation regarding the detailed mechanisms of induction of apoptosis by knockdown of DLL3 in GI‐NEC cells is necessary. In addition, the effects of ROVA‐T in GI‐NEC cells should be investigated in consideration of the location of DLL3 expression . The findings of this study may contribute to a breakthrough in therapeutic strategies for GI‐NEC.…”

Section: Discussionmentioning

confidence: 94%

Delta‐like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy

et al. 2019

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Delta‐like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A‐positive gastric cancer specimens. Real‐time quantitative RT‐PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno‐electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.

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“…The plethora of ligands regulating NOTCH receptors have been extensively studied in different tumour types because of their onco-regulatory effects [77,78,79]. Depending on the biological microenvironment, the activation of NOTCH signalling seems to have a dual role, showing an oncogenic activity in certain tissues (i.e., the non-neuroendocrine component of small cell lung cancer) [73,80], and tumour-suppressor function in others (i.e., medullary thyroid carcinoma, small cell lung cancer, pancreatic and biliary neuroendocrine tumours) [81,82,83,84].…”

Section: Structure Of Notch Receptors and The Notch Signalling Patmentioning

confidence: 99%

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms

Arx

Capozzi

López‐Jiménez

et al. 2019

JCM

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Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies, mainly originating from hormone-secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout the multiple endocrine neoplasia type 1 (MEN-1) gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signalling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the role and the potential therapeutic implications of gene mutations and NOTCH signalling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential role across all NEN subtypes is required.

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DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail

Cited by 53 publications

References 41 publications

Combination therapy: Future directions of immunotherapy in small cell lung cancer

Combination therapy: Future directions of immunotherapy in small cell lung cancer

Delta‐like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms

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