Customizing Cisplatin Based on Quantitative Excision Repair Cross-Complementing 1 mRNA Expression: A Phase III Trial in Non–Small-Cell Lung Cancer

Cobo, Manuel; Isla, Dolores; Massutí, Bartomeu; Montes, Ana; Sánchez, José Miguel; Provencio, Mariano; Viñolas, Núria; Paz‐Ares, Luis; López-Vivanco, G.; Muñóz, Miguel Ángel Suárez; Felip, Enriqueta; Alberola, Vicente; Camps, Carlos; Dómine, Manuel; Sánchez, José Javier; Sanchez-Ronco, María; Danenberg, Kathleen D.; Tarón, Miquel; Gandara, David R.; Rosell, Rafael

doi:10.1200/jco.2006.09.7915

Cited by 426 publications

(293 citation statements)

References 25 publications

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“…Other studies showed that the low intratumoral ERCC1 mRNA expression was associated with favorable clinical outcomes after treatment with platinum-based chemotherapy in lung cancer [27,28] , colorectal cancer [29] , gastric cancer [30][31][32] , ovarian cancer [33] , bladder cancer [34] , head and neck cancer [35] . A recent phase Ⅲ trial in nonsmall-cell lung cancer also demonstrated that assessment of intratumoral ERCC1 mRNA expression is feasible in the clinical setting and predicts response to cisplatin [36] . However, most of those studies focused on the influence of ERCC1 expression on the effect of platinum-drug in advanced or metastatic diseases, little was known about its effect on platinum-drug adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Huang¹,

Dong²,

Du³

et al. 2008

WJG

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in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P < 0.05).CONCLUSION: ERCC1 codon 118 polymorphism has no significant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy. INTRODUCTIONIn China, gastric cancer is the leading cause of cancer deaths, accounting for nearly one-fourth of all cancer deaths. Surgery is the primary modality for managing early-stage and locally-advanced disease. However, even after gastrectomy, the majority of patients develop local or distant recurrence [1] . Adjuvant chemotherapy for gastric cancer has been under clinical investigation for more than four decades. Fluoropyrimidines, platinumdrugs and taxanes were shown to be effective in the treatment of gastric cancer. However, the response rates of these drugs or their combinations were less than 50% [2,3] . There is no standard regimen for postoperative treatment at the moment. Having an effective assay to predict the response to a given chemotherapeutic protocol beforehand would greatly enhance the success rate as well as the life quality of the patients.The nucleotide excision repair (NER) system plays a significant role in repairing a variety of distorting Abstract AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1 ) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P < 0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival

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Section: Discussionmentioning

confidence: 99%

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Huang¹,

Dong²,

Du³

et al. 2008

WJG

View full text Add to dashboard Cite

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“…Analysis on mRNA expression results of ERCC1 gene demonstrated that 40.00% pertained to low expression in postoperative patients with NSCLC, suggesting that 40.00% of patients with NSCLC are sensitive to platinum chemotherapy, but the resistance to drugs is not dependent on the expression level of one gene or protein at all (Cobo et al, 2007). On the other hand, the detection of expression quantity to this gene can preliminarily screen out a part of patients with drug resistance so as to guide clinical administration better.…”

Section: Discussionmentioning

confidence: 99%

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

Han

Wang²,

Xiao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: To explore mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in tumor tissue of postoperative patients with non-small cell lung cancer (NSCLC). Materials and Methods: Sixty NSCLC patients undergoing radical operation in our hospital from Nov., 2011 to Jun., 2012 were selected. Plasmid standards of ERCC1, BRCA1, RRM1, TYMS and TUBB3 were established and standard curves were prepared by SYBR fluorescent real-time quantitative PCR analysis. Samples from tumor centers were taken to detect mRNA expression of ERCC1, BRCA1, RRM1, TYMS and TUBB3 genes in cancerous tissue during operation. The total mRNA expression quantities were compared according to different clinical characteristics. Results: The total expression quantities of 5 genotypes from high to low were ERCC1>RRM1>TUBB3>TYMS>BRCA1 in turn. By pairwise comparisons, other differences showed statistical significance (p<0.05 or p<0.01) except for TYMS and TUBB3 (p>0.05); the low expression rates from high to low were ERCC1>TYMS>TUBB3>TUBB3>RRM1>BRCA1 in turn. The expression quantities of BRCA1, RRM1 and TYMS in males, smokers and patients without adenocarcinoma were all significantly higher than that in females, non-smokers and patients with adenocarcinoma, and significant differences were present (p<0.05 or p<0.01). In terms of pathological staging, the expression quantities of BRCA1, RRM1 and TYMS in phases Ⅱa~Ⅱb and Ⅲa~Ⅲb had a tendency to be greater than in phases Ⅰ and Ⅳ. Conclusions: Resistance to chemotherapy and sensitivity to targeted therapy differ among patients with NSCLC. Differences in gene expression in different individuals were also revealed. Only according to personalized detection results can individualized therapeutic regimens be worked out, which is a new direction for oncotherapy.

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“…45,46 In the only prospective randomized clinical trial testing customized chemotherapy in advanced NSCLC, ERCC1 mRNA predicted for response to cisplatin-based chemotherapy in 346 patients. 47 Some researchers have demonstrated that in earlystage NSCLC surgically resected for cure, ERCC1 expression was also prognostic in favor of longer survival. [48][49][50] However, the finding was not confirmed in all studies.…”

Section: Discussionmentioning

confidence: 99%

The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer

Weberpals

Garbuio²,

O'Brien³

et al. 2008

Intl Journal of Cancer

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This study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum-based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p 5 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p 5 0.03). There was a non-significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p 5 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro. ' 2008 Wiley-Liss, Inc.Key words: BRCA1; ERCC1; sporadic ovarian cancer; DNA repair; predictive marker Epithelial ovarian cancer (OC) is generally diagnosed at advanced stage resulting in a 5-year survival of only 20-30%. The standard treatment of OC is surgical debulking followed by platinum and taxane chemotherapy. Although 70% of patients with advanced disease initially respond to the first-line regimen, early recurrences and platinum resistance are common obstacles in the management of this disease. Identifying reliable predictors of response and the use of novel therapeutic agents to enhance platinum efficacy are needed to improve the management of OC. Platinum resistance is multifactorial, 1 and an important mechanism of resistance is increased tolerance to platinum-DNA damage and enhanced repair of damaged DNA. In a variety of malignancies including OC, enhanced expression of the DNA repair proteins, Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1), have correlated with resistance to platinum. [2][3][4][5][6] In vitro models have shown that targeting the expression of both BRCA1 and ERCC1 sensitizes cells to platinum-based chemotherapeutic agents, suggesting a potential clinical application to help overcome platinum resistance in OC.Mutations in the BRCA1 tumor suppressor gene are ...

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Customizing Cisplatin Based on Quantitative Excision Repair Cross-Complementing 1 mRNA Expression: A Phase III Trial in Non–Small-Cell Lung Cancer

Cited by 426 publications

References 25 publications

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

mRNA Expression and Clinical Significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in Postoperative Patients with Non-Small Cell Lung Cancer

The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer

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