Does <i>MDR-1</i> G2677T/A Polymorphism Really Associate with Ovarian Cancer Response to Paclitaxel Chemotherapy?

Ludwig, Agnieszka H.; Kupryjańczyk, Jolanta

doi:10.1158/1078-0432.ccr-06-1374

Cited by 11 publications

(5 citation statements)

References 3 publications

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“…The number of mutated alleles were also shown to influence the response which improved with increasing number of variant alleles 12. Two groups later published results from similar studies, but with different outcome 13, 14. However, the differences might be explained by variations in the composition and/or subdivision of tumor material and/or patients 16 .…”

Section: Discussionmentioning

confidence: 96%

“…Recently, we showed that the SNP G2677T/A correlated with the response to paclitaxel treatment in ovarian cacner,12 although other studies have given different results 13, 14. The importance of P‐gp transport for the effects of paclitaxel treatment, our previous findings and the shown impact of the G1199T/A SNP on the in vitro resistance led us to investigate the clinical importance of this SNP during paclitaxel treatment of ovarian cancer.…”

Section: Introductionmentioning

confidence: 93%

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ABCB1 G1199A Polymorphism and Ovarian Cancer Response to Paclitaxel

Gréen

Söderkvist

Rosenberg

et al. 2008

Journal of Pharmaceutical Sciences

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P-glycoprotein, encoded by the ABCB1 gene, confers multi-drug resistance to a variety of antineoplastic agents, e.g. paclitaxel. Recently, the G1199T/A polymorphism in the ABCB1 gene was shown to be important for the function of P-glycoprotein as well as for the resistance to several chemotherapeutic agents in vitro. We analyzed the allelic distribution of the G1199T/A and other polymorphisms in exons 11 and 12 of the ABCB1 gene in ovarian cancer patients treated with paclitaxel and carboplatin in order to evaluate their predictive value in vivo. The SNPs C1236T, G1199T/A and A1308G were determined using Pyrosequencing in 51 patients with advanced ovarian cancer and correlated to the progression free survival. The G1199T/A SNP was found to affect the progression free survival. Although only two heterozygous (G/A) patients were found their mean progression free survival was only 2 months as compared to 19 months for the wild-type patients. This is in accordance with the higher resistance for the 1199A genetic variant found in vitro. Genotyping of the ABCB1 gene may be important for determining the tumor resistance to paclitaxel and provide useful information for individualized therapy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 93%

ABCB1 G1199A Polymorphism and Ovarian Cancer Response to Paclitaxel

Gréen

Söderkvist

Rosenberg

et al. 2008

Journal of Pharmaceutical Sciences

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“…Originally, it was found that individuals carrying ABCB1 2677G>T/A variants had a moderately significant improved progression free survival after paclitaxel therapy (33). However, a follow-up study in a larger patient population was unable to replicate their observations (34), and a later study found that individuals carrying 2677G>T/A variants actually had a 2.5 times higher risk of death following paclitaxel therapy (35). It is therefore possible that alterations in dosage, schedule, patient selection, and concomitant medications can alter the relationship between survival after taxane treatment and ABCB1 genotype status.…”

Section: Discussionmentioning

confidence: 99%

ABCB1 Genetic Variation Influences the Toxicity and Clinical Outcome of Patients with Androgen-Independent Prostate Cancer Treated with Docetaxel

Sissung

Baum

Deeken

et al. 2008

Clinical Cancer Research

120

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Purpose: Polymorphisms that are associated with ABCB1expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. Experimental Design: Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm.The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. Results: For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). Conclusion:The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.

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“…Reversal of MDR in ovarian cancer cell lines is possible with siRNA knockout of ABCB1 (MDR1) and ABCB4 (MDR3) genes [410, 411], combination drug treatments [412, 413], chitosan/pshRNA plasmid nanoparticle targeting of MDR1 genes [414], and perturbation of P-glycoprotein N-glycosylation [415]. The prognostic value of ABCB1 gene polymorphisms in ovarian cancer patients is conflicting, for example, whereas a recent study found that ABCB1 G2677T/A and ABCB1 C3435T gene polymorphisms did not correlate with survival and prognosis in Caucasian women with ovarian cancer [416, 417], another study found such a relationship [418]. Analogous earlier reports concluded that although MDR1 expression profiles may be closely related to histologic subtype of ovarian cancer, they were not accurate predictors of survival [419, 420].…”

Section: Ovarian Cancer Biomarkers and Cellsignaling Pathwaysmentioning

confidence: 99%

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

Hiss

2012

Journal of Oncology

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The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales.

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Does MDR-1 G2677T/A Polymorphism Really Associate with Ovarian Cancer Response to Paclitaxel Chemotherapy?

Cited by 11 publications

References 3 publications

ABCB1 G1199A Polymorphism and Ovarian Cancer Response to Paclitaxel

ABCB1 G1199A Polymorphism and Ovarian Cancer Response to Paclitaxel

ABCB1 Genetic Variation Influences the Toxicity and Clinical Outcome of Patients with Androgen-Independent Prostate Cancer Treated with Docetaxel

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

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