Notch pathway inhibition mediated by arsenic trioxide depletes tumor initiating cells in small cell lung cancer

Yang, Mian; Li, Bing; Chang, Ke-Jie

doi:10.1007/s11033-021-07046-w

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…Although the mechanism for this is unclear, some theories support this hypothesis. The existence of cancer stem cells, being related to the differentiation and proliferation of cancer cells, were supposed to have ability to differentiate into either SCLC or NSCLC (16)(17)(18)(19)(20). Lung adenocarcinoma and SCLC were found to have the potential shared cell of origin.…”

Section: Discussionmentioning

confidence: 99%

Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report

Yang

Cai

et al. 2022

Front. Oncol.

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BackgroundHistological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of mechanisms of the acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). However, SCLC transformation and tumor heterogeneity have never been reported in sequential targeted therapy and immunotherapy.Case presentationHere, we described a patient with advanced EGFR-mutant NSCLC, who received erlotinib and underwent the resistance with EGFR T790M (–). The patient then received chemotherapy plus immunotherapy of programmed cell death 1 (PD-1) inhibitor, encountered progression with pathological transformation from NSCLC to SCLC that was overcome by chemotherapy of etoposide plus carboplatin (EC) with the main lesion significantly shrinking while metastatic nodules increasing. The pathology of the metastatic nodule showed NSCLC with EGFR T790M (+). Based on the tumor heterogeneity, EC chemotherapy combined with osimertinib was used, and patients responded well. The patient experienced four lung biopsies in all, which helped to provide the patient with precise treatment.ConclusionsThis case suggested that SCLC transformation and tumor heterogeneity should be paid attention to when disease progression occurred in advanced NSCLC whether receiving targeted therapy or immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report

Yang

Cai

et al. 2022

Front. Oncol.

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“…Mib1 ubiquitinates and induces the degradation of survival of motor neuron proteins (SMNs), and Mib1 knockdown increases SMN protein levels in HEK-293T cells, suggesting a beneficial effect on the survival of motor neurons [ 131 ]. Similar to Mib1 mutation, arsenic has been shown to block Notch signaling in a human small-cell lung cancer cell line [ 132 , 133 ]. Whether arsenic inhibits Notch signaling in zebrafish, which could be responsible for the neurogenic phenotype we have reported [ 76 ], warrants further studies that would reveal divergent or convergent pathways linking the phenotypes to the upstream events.…”

Section: Cdk5 Knockdown and Zebrafish Motor Neurons: Relevance To Autismmentioning

confidence: 99%

Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism

Gu,

Kanungo

2024

IJMS

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The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism.

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“…For instance, by down-regulated NOTCH pathway, arsenic trioxide (As2O3) treatment could inhibit SCLC TIC proliferation, sphere formation, and clonogenic capacity [27]. Additionally, immune checkpoint blockade (ICB) benefits only a small subset of patients with SCLC.…”

Section: Targeting the Notch Signaling Pathway In Lung Cancermentioning

confidence: 99%

“…Indeed, the extent of stemness within NSCLC tumors seems to be, on average, less than that of SCLC and deregulated NOTCH pathway is perhaps a more significant event for SCLC [16 ▪▪ ,26 ▪▪ ]. For instance, by down-regulated NOTCH pathway, arsenic trioxide (As2O3) treatment could inhibit SCLC TIC proliferation, sphere formation, and clonogenic capacity [27]. Additionally, immune checkpoint blockade (ICB) benefits only a small subset of patients with SCLC.…”

Section: Targeting the Notch Signaling Pathway In Lung Cancermentioning

confidence: 99%

Targeting cancer stem cell pathways for lung cancer therapy

Liu

2022

Current Opinion in Oncology

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Purpose of reviewThe unique properties of cancer stem cells (CSCs) make lung cancer untargetable for quite an extended period. The functional mechanism of this cell type has been illustrated step by step. However, the outcomes of lung cancer patients are still lower than expected clinically. The attempts made by scientists to make challenge history against stemness maintenance of lung cancer cells and their druggable targets are worth elucidating. Recent findingsMany agents, including the Bispecific T-cell engager (BiTE) and AMG 119 targeting DLL3-positive cells, are a tremendous breakthrough in the preclinical and clinical treatment of SCLC. More studies focus on targeting CSCs to overcome TKI resistance in NSCLC. The combo targeting of CSC and the immune microenvironment can favor the treatment of lung cancer patients.

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Notch pathway inhibition mediated by arsenic trioxide depletes tumor initiating cells in small cell lung cancer

Cited by 7 publications

References 26 publications

Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report

Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report

Neurogenic Effects of Inorganic Arsenic and Cdk5 Knockdown in Zebrafish Embryos: A Perspective on Modeling Autism

Targeting cancer stem cell pathways for lung cancer therapy

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