ERCC1 and BRAC1 mRNA Expression Levels in the Primary Tumor Could Predict the Effectiveness of the Second-Line Cisplatin-Based Chemotherapy in Pretreated Patients with Metastatic Non-small Cell Lung Cancer

Papadaki, Chara; Sfakianaki, Maria; Ioannidis, Georgios; Lagoudaki, Eleni; Trypaki, Maria; Tryfonidis, K.; Mavroudis, Dimitris; Stathopoulos, Efstathios N.; Georgoulias, Vassilis; Souglakos, John

doi:10.1097/jto.0b013e318244bdd4

Cited by 54 publications

(53 citation statements)

References 44 publications

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“…Of the 13 included studies, 4 were for non-small-cell lung cancer, 3 were for breast cancer, and 2 were for ovarian cancer; the remaining four were for malignant pleural mesothelioma, esophageal squamous cell carcinoma, small cell lung cancer and gastric cancer. Of the 13 studies, 7 were from an EastAsian population (14,(16)(17)(18)(19)(20)24), the other 6 studies were from a European population (5,7,15,(21)(22)(23). Characteristics of included studies are summarized in Table S1.…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

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Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

Zhang

Zhang³

et al. 2016

Ann. Transl. Med.

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Background: Breast cancer susceptibility gene 1 (BRCA1) expression has been suggested as a predictor in antineoplastic treatment with anti-microtubule agents. However, the existing evidence is conflicting. Consulting the literature, we sought to examine the true impact of BRCA1 expression on the efficacy of anti-microtubule agents.Methods: Medline by PubMed and Embase databases were searched for eligible studies. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Additional subgroup analyses stratified for detection methods, regimen, and patient origin were also performed.Results: A total of 13 relevant studies involving a total of 1,490 cases were enrolled. Involved agents included paclitaxel, docetaxel and vinorelbine; Malignancies included non-small cell lung cancer, gastric cancer, esophageal carcinoma, ovarian carcinoma, malignant pleural mesothelioma, breast cancer, and small cell lung cancer. Through meta-analyses, we observed a potentially greater ORR in the population with high BRCA1 expression vs. low BRCA1 expression (OR 1.63, 95% CI: 0.92 to 2.88, P=0.09) but the heterogeneity is severe (P=0.01; I 2 =61%). Similar results were observed in PFS (high vs. low expression, HR 0.93, 95% CI: 0.75 to 1.15, P=0.49; heterogeneity, P<0.01, I 2 =75%). After stratification by testing methods, a significantly higher ORR in the population with high BRCA1 expression was shown in the subgroup using mRNA as a quantitative method (OR 2.90, 95% CI: 1.92 to 4.39, P<0.01; I 2 =0) whereas the difference in the subgroup using immunohistochemistry (IHC) was not significant (OR 0.60, 95% CI: 0.33 to 1.10, P=0.10; I 2 =0). Stratification by regimen (platinum-based vs. non platinum-based) and patient origin (Asian vs. Caucasian) did not reduce the heterogeneity. Conclusions:Although the predictive value of BRCA1 expression on the anti-microtubule chemotherapy remained uncertain based on overall results, our exploratory analyses suggested that detection using mRNA might be a preferred technique, however, further validation is required to substantiate our findings.

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Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

“…Figure 1 summarizes the flow chart. Among these studies, the object response rate (ORR) was provided in 9 studies (5,7,(14)(15)(16)(17)(18)(19)(20), the remaining 4 studies provided only OS or PFS (21)(22)(23)(24). Characteristics of all involved studies are summarized in Table S1.…”

Section: Eligible Studiesmentioning

confidence: 99%

Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

Zhang

Zhang³

et al. 2016

Ann. Transl. Med.

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“…Rate-limiting role in the nucleotide excision repair pathway that recognises and removes cisplatin DNA adducts Alterations in ERCC1 expression levels ERCC1 mRNA levels predict sensitivity to cisplatin [86,87] Hazard ratio: 0.6 [87] Low expression Increased sensitivity to PARP inhibitors [88] rs3212986 A Significantly associated with increased risk of death from NSCLC [ …”

Section: Arg 194 Trpmentioning

confidence: 99%

DNA Repair Pathways and their Therapeutic Potential in Lung Cancer

Burgess

Croft

Wallace

et al. 2014

Lung Cancer Manage.

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practice points• A normal cycling cell can encounter up to 30,000 DNA damage events in 1 day, which are repaired by distinct pathways that target and repair specific lesions.• Platinum-based chemotherapeutics exert toxicity through the formation of irreparable base adducts and DNA crosslinks, which direct the cancerous cells towards apoptotic death.• The selective pressure exerted on the tumor eventuates genetic drift and may provide the cancerous cells resistance to many anticancer therapies.• Several distinct while overlapping pathways exist within the cell to detect and repair the various DNA damage lesions that may occur.• The inaccurate repair of DNA lesions may lead to mutations within the cell and drive tumorigenesis.• Many cancers contain mutations in DNA repair genes, for example, more than 90% of small cell lung cancers and 50% of all non-small-cell lung cancers carry mutations in tP53, encoding the important tumor suppressor, p53.• Many anticancer therapies, including platinum-based chemotherapeutics and replication inhibitors, induce apoptosis within the cell through the formation of irreparable DNA damage.• The deregulation of DNA repair proteins within cells may provide an attractive therapeutic window. Such an approach is exemplified by the PARP inhibitors, which show potential use in the treatment of cancers deficient of functional BRCA1 or BRCA2. In addition, these drugs may show increased efficacy in combination with DNA-damaging agents.• Resistance to platinum-based agents may be acquired through multiple mechanisms, including mutation or deregulation of DNA repair proteins, alteration of membrane transport protein activity and chromatin remodeling.

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“…With the development of pharmacogenomics and pharmacogenetics, tumor heterogeneity is considered to be a significant factor that is responsible for the failure of conventional chemotherapeutics (6,7). In predictive biomarker studies, a number of genes have been reported to predict response to chemotherapy for solid tumors, including excision repair cross-complementation group 1 (ERCC1), breast cancer type 1 gene (BRCA1) or ADP ribosylation factor like GTPase 6 interacting protein 5 (JWA) for cisplatin (8), BRCA1, tubulin β-3 class III (TUBB3) or F-box and WD repeat domain containing 7 (FBW7) for docetaxel (9)(10)(11), thymidylate synthetase (TS) for fluorouracil (12), and ribonucleotide reductase catalytic subunit M1 (RRM1) for gemcitabine (13), murine double minute 2 (MDM2) for etoposide (14) and DNA topoisomerase 1 (TOP1) for irinotecan (15). Additionally, a few of the genes, including BRCA1, JWA and TS, have been validated for their clinical value in esophageal cancer (8,12).…”

Section: Introductionmentioning

confidence: 99%

“…In predictive biomarker studies, a number of genes have been reported to predict response to chemotherapy for solid tumors, including excision repair cross-complementation group 1 (ERCC1), breast cancer type 1 gene (BRCA1) or ADP ribosylation factor like GTPase 6 interacting protein 5 (JWA) for cisplatin (8), BRCA1, tubulin β-3 class III (TUBB3) or F-box and WD repeat domain containing 7 (FBW7) for docetaxel (9)(10)(11), thymidylate synthetase (TS) for fluorouracil (12), and ribonucleotide reductase catalytic subunit M1 (RRM1) for gemcitabine (13), murine double minute 2 (MDM2) for etoposide (14) and DNA topoisomerase 1 (TOP1) for irinotecan (15). Additionally, a few of the genes, including BRCA1, JWA and TS, have been validated for their clinical value in esophageal cancer (8,12). However, the clinical value of the aforementioned biomarkers for chemotherapeutic agents such as irinotecan (16), gemcitabine (5) and etoposide (17), which are not commonly used but exhibit moderate activity for treating esophageal cancer, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer

et al. 2017

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Abstract. Personalized chemotherapy with the use of biomarkers helps to maximize clinical efficiency. Therefore, the present study aimed to identify a potential method for identifying biomarkers in esophageal cancer. A total of 49 freshly resected tumor tissues and 72 paraffin-embedded specimens from patients with esophageal cancer were obtained. mRNA expression levels of ERCC1, BRCA1, TUBB3, FBW7, RRM1, MDM2, TS and TOP1 were measured quantitative reverse transcription polymerase chain reaction (RT-qPCR). In vitro chemosensitivity to cisplatin, docetaxel, gemcitabine, etoposide, fluorouracil and irinotecan were tested using histoculture drug response assay (HDRA). BRCA1 mRNA levels were positively correlated with resistance to cisplatin (P= 0.027) and sensitivity to docetaxel (P=0.002). TS mRNA levels were inversely correlated with fluorouracil sensitivity (P= 0.044), and TOP1 mRNA expression was positively correlated with irinotecan sensitivity (P= 0.008). In addition, high BRCA1 mRNA levels correlated with decreased median overall survival (mOS; P<0.001) and response rate (RR; P= 0.002) in cisplatin-fluorouracil chemotherapy group and also correlated with increased mOS (P<0.001) and RR (P= 0.023) in docetaxel-fluorouracil chemotherapy group. Overall, these results suggested that HDRA combined with RT-qPCR may serve as an effective method for screening biomarkers in personalized chemotherapy for esophageal cancer.

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ERCC1 and BRAC1 mRNA Expression Levels in the Primary Tumor Could Predict the Effectiveness of the Second-Line Cisplatin-Based Chemotherapy in Pretreated Patients with Metastatic Non-small Cell Lung Cancer

Abstract: These results suggest that the ERCC1 and BRCA1 mRNA expression levels in the primary tumor at the time of diagnosis could be used for the prediction of platinum sensitivity in the treatment of NSCLC in the second-line setting. Cross-validation studies are warranted.

Cited by 54 publications

References 44 publications

Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

DNA Repair Pathways and their Therapeutic Potential in Lung Cancer

Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer

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