Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

He, Yijing; Winham, Stacey J.; Hoskins, Janelle M.; Glass, Stephanie; Paul, Jim; Brown, Robert E.; Motsinger‐Reif, Alison A.; McLeod, Howard L.

doi:10.1038/tpj.2015.52

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…As for ATP7B , ATP7B rs9535828 A allele and rs9535826 G allele carriers had better treatment outcome of platinum‐based chemotherapy in NSCLC patients . In addition, ATP7B rs1061472 and rs1801249 were reported to be significantly associated with carboplatin/taxane‐induced gastrointestinal toxicity in ovarian cancer patients . These findings show that ATP7A and ATP7B may be potential biomarkers to predict the response to platinum‐based chemotherapy.…”

Section: Atp7a/7b and Platinum Drug Resistancementioning

confidence: 76%

“…ATP7A rs2227291 was found to be associated with cisplatin resistance in epithelial ovarian cancer patients (44). However, no ATP7A polymorphisms were observed to be associated with carboplatin/taxane-induced gastrointestinal toxicities in ovarian cancer patients (45). As for ATP7B, ATP7B rs9535828 A allele and rs9535826 G allele carriers had better treatment outcome of platinum-based chemotherapy in NSCLC patients (46).…”

Section: Atp7a/7b and Platinum Drug Resistancementioning

confidence: 97%

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Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy

Yin

Liu

et al. 2018

IUBMB Life

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Platinum-based chemotherapy agents are widely used in the treatment of various solid malignancies. However, their efficacy is limited by drug resistance. Recent studies suggest that copper efflux transporters, which are encoded by ATP7A and ATP7B, play an important role in platinum drug resistance. Over-expressions of ATP7A and ATP7B are observed in multiple cancers. Moreover, their expressions are associated with cancer prognosis and treatment outcomes of platinum-based chemotherapy. In our review, we highlight the roles of ATP7A/7B in platinum drug resistance and cancer progression. We also discuss the possible mechanisms of platinum drug resistance mediated by ATP7A/7B and provide novel strategies for overcoming resistance. This review may be helpful for understanding the roles of ATP7A and ATP7B in platinum drug resistance. © 2018 IUBMB Life, 70(3):183-191, 2018.

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Section: Atp7a/7b and Platinum Drug Resistancementioning

confidence: 76%

Section: Atp7a/7b and Platinum Drug Resistancementioning

confidence: 97%

Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy

Yin

Liu

et al. 2018

IUBMB Life

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“…It has been shown that single nucleotide polymorphisms (SNPs) might affect gene expression and function, accounting for interindividual differences in drug efficacy and toxicity 18 , 19 . A few ATP7B SNPs have been reported possible role in chemotherapeutic toxicity 20 , 21 . However, less is known about the effects of SNPs on the expression level of ATP7B and the response to platinum-based chemotherapy in NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Gene expression and single nucleotide polymorphism of ATP7B are associated with platinum-based chemotherapy response in non-small cell lung cancer patients

Li¹,

Chen²,

Yin³

et al. 2018

J. Cancer

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Objectives: Platinum-based chemotherapy is first-line treatment for non-small cell lung cancer (NSCLC) patients. The efficacy is limited by drug resistance. Recent studies suggest that ATP7B, a copper efflux transporter, may be involved in platinum resistance. However, the clinical significance of ATP7B expression in NSCLC is controversial. Moreover, the effects of single nucleotide polymorphisms (SNPs) in ATP7B gene on the response to platinum-based chemotherapy are scarcely understood. The aim of our study is to evaluate the clinical value of ATP7B in NSCLC patients and explore the interrelationships between ATP7B SNPs and protein expression, and their association with chemotherapy response.Materials and Methods: A total of 247 NSCLC patients were recruited in this study. Among them, 158 patients who received platinum-based chemotherapy were used to explore the interrelationships between ATP7B SNPs, protein expression and chemotherapy response, while 89 patients who underwent surgical resection were used to further investigate the association between ATP7B SNPs and expression level. We genotyped 15 SNPs of ATP7B by Sequenom MassARRAY and determined ATP7B protein levels by immunohistochemistry.Results: Patients with ATP7B-negative tumors had improved chemotherapeutic response (p=0.025) and better overall survival (p=0.044) compared with the patients with ATP7B-positive tumors. The multivariate Cox regression analysis revealed that ATP7B expression was an independent prognostic factor (HR=0.639, 95%CI=0.424-0.962, p=0.032). Moreover, we found that the rs9526814 GG genotype was significantly associated with favorable response to platinum-based chemotherapy when compared with TT+TG genotypes (OR=0.362, 95CI%=0.140-0.935, p=0.036). Mechanistically, rs9526814 GG genotype showed a strong trend towards reduced expression level of ATP7B compared with the TT+TG genotypes (p= 0.048).Conclusion: Our findings indicate that ATP7B rs9526814 may contribute to platinum resistance by influencing ATP7B gene expression and can be used as a potential biomarker to predict the sensitivity of platinum-based chemotherapy in NSCLC patients.

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“…For instance, patients with advanced OVCA develop recurrent disease and die within 5 years due to development of resistance to platinum‐based chemotherapy (Raja et al, ). In addition, standard platinum–taxane doublet chemotherapy is associated with several adverse side effects including gastrointestinal toxicity (He et al, ), febrile neutropenia and peripheral neuropathy (Wang et al, ), and other non‐hematological toxicities (Shawky et al, ).…”

mentioning

confidence: 99%

Epithelial‐to‐Mesenchymal Transition in Paclitaxel‐Resistant Ovarian Cancer Cells Is Downregulated by Luteolin

Dia

Pangloli

2016

Journal Cellular Physiology

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Ovarian cancer (OVCA) is the deadliest of all gynecological cancers which is attributed to late presentation, persistence, and development of chemoresistance. The objectives were to evaluate the association between OVCA paclitaxel-resistance and epithelial-to-mesenchymal transition (EMT) and to determine the capability of luteolin to chemosensitize OVCA cells. X10 and X22 cells were 11.8-25.3-fold and 7.8-8.6-fold resistant to paclitaxel than 1AP cells. X10 and X22 cells exhibited a mesenchymal phenotype, while 1AP has an epithelial characteristics. Furthermore, the expression of the epithelial marker E-cadherin was downregulated, while mesenchymal markers Vimentin and N-cadherin were upregulated in X10 and X22 cells when compared to 1AP cells. Transcription factors Snail, Slug, and Twist1 were upregulated in X10 cells, while Twist1 was highly expressed in X22 cells. Luteolin treatment caused cytotoxicity being most potent to X10 OVCA cells. Treatment of non-cytotoxic dose of luteolin at 15.625 μM chemosensitized X10 and X22 OVCA cells to paclitaxel as evidenced by reduced ED values from 11.8 to 0.2 μM and 8.6 to 3.6 μM for X10 and X22 cells, respectively. Moreover, luteolin treatment led to a more epithelial phenotype of X10 and X22 cells and modification of EMT markers indicating reversal of EMT. The mechanism involved is through reduction of phosphorylation of FAK and ERK leading to reduced nuclear translocation of p65. Our results highlight the significance of EMT in OVCA resistance to paclitaxel and warrant the investigation of luteolin as a potential therapeutic agent in chemoresistant OVCA. J. Cell. Physiol. 232: 391-401, 2017. © 2016 Wiley Periodicals, Inc.

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Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Cited by 13 publications

References 26 publications

Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy

Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy

Gene expression and single nucleotide polymorphism of ATP7B are associated with platinum-based chemotherapy response in non-small cell lung cancer patients

Epithelial‐to‐Mesenchymal Transition in Paclitaxel‐Resistant Ovarian Cancer Cells Is Downregulated by Luteolin

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