Platinum versus non-platinum chemotherapy regimens for small cell lung cancer

Amarasena, I; Chatterjee, Saion; Walters, Julia; Wood‐Baker, Richard; Fong, Kwun M.

doi:10.1002/14651858.cd006849.pub3

Cited by 49 publications

(28 citation statements)

References 57 publications

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“…The standard of care for SCLC is platinum-based combination chemotherapy, using either etoposide or irinotecan, in association with radiotherapy in limited stage disease (LS-SCLC). There is a typical disease trajectory with an initial good clinical response followed by rapid relapse of chemoresistant tumour and death [4]. Because surgical resection is not part of standard care, SCLC research using primary tumour tissue is limited to small diagnostic samples and, thus, the therapeutic benefits from the molecular analysis of this tumours are limited during the last 30 years [5].…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

et al. 2013

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BackgroundThe aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC).Methods184 SCLC patients’ primary tumour samples were analyzed for ERCCI, BRCA1, ATP7B, PKM2 TOPOI, TOPOIIA, TOPOIIB and C-MYC mRNA expression. All patients were treated with cisplatin-etoposide.ResultsThe patients’ median age was 63 years and 120 (65%) had extended stage, 75 (41%) had increased LDH serum levels and 131 (71%) an ECOG performance status was 0-1. Patients with limited stage, whose tumours expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPOI (p=0.008), TOPOIIA (p=0.002) and TOPOIIB (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPOIIA (p=0.021) and TOPOIIB (p=0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high TOPOIIB expression had a negative impact on Os (p=0.035). The favorable expression signature expression signature (low expression of ERCC1, PKM2, TOPOIIA and TOPOIIB) was correlated with significantly better PFS and Os in both LS-SCLC (p<0.001 and p=0.007, respectively) and ES-SCLC (p=0.007 and (p=0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; p=0.002 and HR: 3.14; p=0.021) and Os (HR: 4.35; p=0.001and HR: 3.32; p=0.019) in both limited and extended stage, respectively.ConclusionsSingle gene’s expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPOIIA and TOPOIIB may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.

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Section: Introductionmentioning

confidence: 99%

Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

et al. 2013

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“…For the past two decades, the standard treatment for these advanced SCLC patients has been combined chemotherapy, comprising treatment with cisplatin and either etoposide or irinotecan. The response rate for this therapy is approximately 70–80%; however, the median survival time is only 9–12 months, and the overall survival rate of SCLC patients with extensive disease at 5 years is only 5–10%, largely due to early relapse and acquired resistance …”

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confidence: 99%

Impact of MET inhibition on small‐cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway

et al. 2017

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Small‐cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Hence, novel therapeutic strategies for the treatment of SCLC are urgently required. Accordingly, several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome. The receptor tyrosine kinase MET is a receptor for hepatocyte growth factor (HGF), and aberrant activation of HGF/MET signaling is known as one of the crucial mechanisms enabling cancer progression and invasion. Here, we found that the HGF/MET signaling was aberrantly activated in chemoresistant or chemorelapsed SCLC cell lines (SBC‐5, DMS273, and DMS273‐G3H) by the secretion of HGF and/or MET copy number gain. A cell‐based in vitro assay revealed that HGF/MET inhibition, induced either by MET inhibitors (crizotinib and golvatinib), or by siRNA‐mediated knockdown of HGF or MET, constrained growth of chemoresistant SCLC cells through the inhibition of ERK and AKT signals. Furthermore, treatment with either crizotinib or golvatinib suppressed the systemic metastasis of SBC‐5 cell tumors in natural killer cell‐depleted SCID mice, predominantly through cell cycle arrest. These findings reveal the therapeutic potential of targeting the HGF/MET pathway for inhibition, to constrain tumor progression of SCLC cells showing aberrant activation of HGF/MET signaling. We suggest that it would be clinically valuable to further investigate HGF/MET‐mediated signaling in SCLC cells.

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“…Most patients with SCLC present with metastatic disease . Although SCLC is considered highly responsive to first‐line platinum‐based chemotherapy, with the response rate of 70%‐80%, relapse often occurs within 2 years and the overall survival (OS‐relevant) rate beyond 5 years is only 3%‐8% . Besides, SCLC patients have not been received a benefit of the recently developed molecular targeted treatment.…”

Section: Introductionmentioning

confidence: 99%

A three microRNA‐based prognostic signature for small cell lung cancer overall survival

Xin

et al. 2018

J of Cellular Biochemistry

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Background Small‐cell lung cancer (SCLC) is one of the most aggressive cancers with mechanisms far from understood. Objective We proposed to identify valuable prognostic signature for SCLC prognosis prediction. Methods microRNA (miRNA) expression profiles of 42 SCLC patients were acquired from the Gene Expression Omnibus. miRNAs that significantly associated with SCLC overall survival (OS‐relevant) were identified through univariate Cox regression analysis followed by random survival forest analysis for identification of more reliable miRNA signature. Results Eleven OS‐relevant miRNAs were obtained, and hsa‐miR‐194, hsa‐miR‐608, and hsa‐miR‐9 were further refined through RFS. A formula composed of the three miRNAs’ expression values weighted by their multivariate Cox regression coefficients was constructed, and based on which, SCLC patients with longer OS could be well distinguished from those with shorter OS. Conclusions This study should provide a valuable clue for SCLC prognosis evaluation.

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Platinum versus non-platinum chemotherapy regimens for small cell lung cancer

Cited by 49 publications

References 57 publications

Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

Impact of MET inhibition on small‐cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway

A three microRNA‐based prognostic signature for small cell lung cancer overall survival

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