Targeting the Notch signaling pathway and the Notch ligand, DLL3, in small cell lung cancer

Zhang, Huan; Yang, Yunkai; Li, Xuchang; Chu, Qian

doi:10.1016/j.biopha.2023.114248

Cited by 16 publications

(13 citation statements)

References 99 publications

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“…Studies have confirmed that DLL3 is positively correlated with the expression of ASCL1, and Zhu et al found the expression of DLL3 in all clinicopathological cases of SCLC‐A 30,31 . Currently, it has been found that the target DLL3 has advantages over other therapies affecting Notch signaling 26 …”

Section: Delta‐like Ligandmentioning

confidence: 93%

“…30,31 Currently, it has been found that the target DLL3 has advantages over other therapies affecting Notch signaling. 26 There is an increasing use of T cell-based immunotherapies in cancer patients, and immune checkpoint inhibitors are being developed that target SCLC. In addition, T cell retargeting therapies that use the intrinsic power of the immune system to target DLL3 have provided new ideas for the treatment of SCLC.…”

Section: Delta-like Ligandmentioning

confidence: 99%

“…The DLL3 protein binds to a variety of Notch receptors in different types of tumors and therefore promotes or inhibits tumorigenesis and development during cell proliferation, differentiation, and apoptosis 22–25 . As a result of DLL3 binding to the Notch1 receptor, Notch signaling activation will be inhibited, causing HES1/HEY1 transcription to be upregulated, and ASCL1 inhibited 26 . ASCL1 is a transcription factor required for normal lung neuroendocrine cell growth and development as well as an oncogenic factor in SCLC 27,28 .…”

Section: Delta‐like Ligandmentioning

confidence: 99%

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Advances in new targets for immunotherapy of small cell lung cancer

Zheng,

Liu,

et al. 2023

Thoracic Cancer

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Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first‐line treatment only results in 10‐month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD‐1/PD‐L1 and CTLA‐4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG‐3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.

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Section: Delta‐like Ligandmentioning

confidence: 93%

Section: Delta-like Ligandmentioning

confidence: 99%

Section: Delta‐like Ligandmentioning

confidence: 99%

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Advances in new targets for immunotherapy of small cell lung cancer

Zheng,

Liu,

et al. 2023

Thoracic Cancer

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show abstract

“…Immunotherapies have been investigated to treat patients with metastatic SCLC. Many of these immunotherapies target delta-like ligand 3 (DLL3), which is a notch ligand that is overexpressed on SCLC cells but is expressed in limited amounts on normal cells ( 4 , 5 ). Some of these immunotherapies use bispecific T-cell engagers (BiTEs)—antibodies that can simultaneously bind to an antigen on tumor cells and a surface molecule on T cells to induce tumor lysis ( 6 ), thus harnessing the host’s T-cell immune response to enhance antitumor activity.…”

mentioning

confidence: 99%

DLL3-targeted CAR T-cell therapy in pre-clinical models for small cell lung cancer: safety, efficacy, and challenges

Bellis,

Adusumilli,

Amador-Molina

2024

Transl Lung Cancer Res

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“…Importantly, Saunders and colleagues showed that, unlike normal cells in the body, DLL3 is specifically present at the surface of SCLC cells ( 8 ). The DLL3 gene is a target of the ASCL1 transcription factor ( 9 ), and it is expressed in a large majority of SCLC cases [reviewed in ( 10 )]. DLL3’s role in the biology of SCLC is still poorly characterized, but DLL3 may contribute to Notch signaling ( 11 ) and to SCLC cell migration ( 12 ).…”

mentioning

confidence: 99%