A comprehensive study of polymorphisms in <i>ABCB1, ABCC2</i> and <i>ABCG2</i> and lung cancer chemotherapy response and prognosis

Campa, Daniele; Müller, Phillip; Edler, Lutz; Knoefel, Lena Franziska; Barale, Roberto; Heußel, Claus Peter; Thomas, Michael; Canzian, Federico; Risch, Angela

doi:10.1002/ijc.27567

Cited by 62 publications

(43 citation statements)

References 50 publications

(101 reference statements)

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“…P-gp is encoded by ABCB1 and is considered to mediate MDR by reducing the intracellular accumulation of cytotoxic drugs and compounds. Many types of cancers express high ABCB1 levels and are unresponsive to chemotherapy (43,44); ABCB1 expression has been considered a predictor of poor response to chemotherapy and overall survival (45,46). Our results also indicated that UCUB cells with high expression of CEBPD are strongly resistant to CDDP and paclitaxel because of ABCC2 and ABCB1 activation (Fig.…”

Section: Discussionsupporting

confidence: 59%

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Wang

Chu

et al. 2017

Clinical Cancer Research

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Purpose: Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel for treating urothelial carcinoma of the urinary bladder (UCUB). CDDP cross-resistance has been suggested to develop with paclitaxel, thus hindering successful UCUB treatment. Therefore, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative and may provide an insight in developing novel therapeutic strategy.Experimental Design: Loss-of-function assays were performed to elucidate the role of the EGFR and STAT3 in CDDP-induced CCAAT/enhancer-binding protein delta (CEBPD) expression in UCUB cells. Reporter and in vivo DNA-binding assays were employed to determine whether CEBPD directly regulates ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily C member 2 (ABCC2) activation. Finally, a xenograft animal assay was used to examine the abilities of gefitinib and S3I-201 (a STAT3 inhibitor) to reverse CDDP and paclitaxel sensitivity.Results: CEBPD expression was maintained in postoperative chemotherapy patients, and this expression was induced by CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. Furthermore, the EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Gefitinib and S3I-201 treatment significantly reduced the expression of CEBPD and enhanced the sensitivity of CDDP-resistant UCUB cells to CDDP and paclitaxel.Conclusions: Our results revealed the risk of CEBPD activation in CDDP-resistant UCUB cells and suggested a therapeutic strategy for patients with UCUB or UCUB resisted to CDDP and paclitaxel by combination with either gefitinib or S3I-201.

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Section: Discussionsupporting

confidence: 59%

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Wang

Chu

et al. 2017

Clinical Cancer Research

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“…These results indicated that the ABCC2 genetic variation is an important factor in survival after chemotherapy in SCLC. 33 Although not all the patients in that study were treated with platinum-based chemotherapy, the results were similar to our own in that there was not a significant association between the genotype of SNP rs3109823 in ABCG2 and clinical outcomes.…”

Section: Discussionsupporting

confidence: 85%

Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non–Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy

Kim

Cho

et al. 2015

American Journal of Clinical Oncology

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Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.

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“…ABCC2 was moderately or highly upregulated in 16HBE, A549, L-132, H460, and H727 cells compared with other cell types and lung tissues. In tumor cell lines, ABCC2 mRNA overexpression was associated with resistance to multiple classes of anticancer drugs (Campa et al, 2012). Regarding the ABCC6 and ABCC9 genes, although they were moderately expressed in lung tissues, we failed to detect their mRNAs in most lung cell models.…”

Section: Number Of Genes Differentially Expressed Between Lung Cell Mmentioning

confidence: 76%

Xenobiotic Metabolism and Disposition in Human Lung Cell Models: Comparison with In Vivo Expression Profiles

et al. 2012

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ABSTRACT:Numerous lung cell lines are currently used as in vitro models for pharmacological and toxicological studies. However, no exhaustive report about the metabolic capacities of these models in comparison with those of lung tissues is available. In the present study, we used a high-throughput quantitative real-time reverse transcription-polymerase chain reaction strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in 10 commonly used lung cell lines (

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A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

Cited by 62 publications

References 50 publications

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non–Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy

Xenobiotic Metabolism and Disposition in Human Lung Cell Models: Comparison with In Vivo Expression Profiles

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