ATP binding cassette transporters and drug resistance in breast cancer.

Endocrine Related Cancer ◽

10.1677/erc.0.0100043 ◽

2003 ◽

pp. 43-73 ◽

Cited By ~ 162

Author(s):

F Leonessa ◽

R Clarke

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Primary Cultures ◽

Significant Proportion ◽

Atp Binding ◽

Breast Cancer Patients ◽

Resistance To Chemotherapy ◽

Clinical Drug ◽

Atp Binding Cassette

Resistance to chemotherapy is a critical issue in the management of breast cancer patients. The nature of clinical drug resistance is likely to be multifactorial. However, in the last decade considerable attention has been dedicated to the role played by membrane transporter proteins belonging to the ATP binding cassette protein superfamily, and in particular by the MDR1 product P-glycoprotein (Pgp) and the multidrug resistance protein (MRP1). Heterogeneity of results is a common feature of studies evaluating the expression and prognostic role of these proteins, due to both methodological and biological factors. Nonetheless, Pgp and MRP1 are detected in a significant proportion of untreated breast cancers (on average 40 and 50% respectively, by immunohistochemistry), without a clear and consistent association with cancer stage. Exposure to chemotherapy increases the expression of both proteins. In vitro studies on primary cultures of breast cancer cells obtained at surgery consistently show an association between Pgp (protein) or MDR1 (mRNA) expression and resistance to chemotherapy. However, the correlation with clinical drug resistance is not as well defined. A stronger association of Pgp/MDR1 with response rates has been observed when expression or an increase in expression are detected immediately following chemotherapy. Correlations with prognosis appear more evident in studies using immunohistochemistry, in adjuvant and neoadjuvant settings. Evidence of clinical reversal of drug resistance by verapamil suggests a functional role of Pgp in drug resistance, although the significance of the evidence is generally weakened by poor trial designs. Future studies should take into account the multifactorial nature of drug resistance in breast cancer and use standardized approaches with adequate controls. Expression studies should be complemented by well-designed trials of drug-resistance reversal using target-specific chemosensitizing agents, and relating the results to the levels of expression of the target proteins.

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The Relation of Haplotype ATP-Binding Cassette B1 (ABCB1) and Gluthation S-Transferase P1 (GSTP1) A313G Gene with Hematological Toxicity in Indonesian Breast Cancer Patients Receiving Chemotherapy

Oman Medical Journal ◽

10.5001/omj.2022.36 ◽

2021 ◽

Author(s):

Siti Syarifah ◽

Tri Widyawati ◽

Dita Hasni ◽

Mutiara Indah Sari ◽

Rusdiana Rusdiana ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Frequency Distribution ◽

Patient Characteristics ◽

Rank Test ◽

Hematological Toxicity ◽

Atp Binding ◽

Breast Cancer Patients ◽

Peripheral Leukocytes ◽

Atp Binding Cassette

Objectives: Hematological toxicity induced by chemotherapy is known to be caused by multiple factors, including genetic factors, such as polymorphisms. The polymorphisms may occur in drug efflux transporter proteins and enzymes involved in drug metabolism. In our study, we investigate the incidence of hematological toxicities and its relation to the haplotype ATP-Binding Cassette B1 (ABCB1) which were polymorphism of C1236T, C3435T, G2677T and Glutathione S-Transferase P1 (GSTP1) A313G gene in Indonesian breast-cancer patients who receives anthracycline during chemotherapy. Methods: One hundred and thirty-eight breast-cancer patients in H. Adam Malik Hospital, Medan, Indonesia who were in the inclusion criteria were recruited in this retrospective cohort study. The DNA of patients was extracted from the peripheral leukocytes. Single nucleotide polymorphism (SNP) ABCB1 and GSTP1 were examined by the PCR-RFLP method. Data on patient characteristics and the incidence of hematological toxicity were obtained from patient medical records after three cycles of chemotherapy. Trend of absolute neutrophil count (ANC) and anemia were analyzed using the Friedmann test and the Wilcoxon signed-rank test. The Kruskal-Wallis test was performed to understand the association of ABCB1 and GSTP1 polymorphisms with the incidence of anemia and neutropenia. The frequency distribution of genotypes and alleles were determined using the Hardy-Weinberg Equilibrium (HWE). Results: A decrease of ANC was found after post chemotherapy on cycles 3 (Mean ± SD: 5644.48± 2962.545/mm3 vs 3034.89±2049.635/mm3 ), and the anemia (12.1478±1.50057 gr/dl vs 11.2746± 1.31221 gr/dl) after the patients underwent three chemotherapy cycles (p <0.05). There was no relation between ABCB1 polymorphism, either in each SNP or in the form of haplotype (the combination of more than one SNP) on the incidence of anemia and neutropenia (p> 0.05). In GSTP1 polymorphisms, no correlation between polymorphisms and anemia and neutropenia incidence (p> 0.05) was found. In our study, the ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE (p> 0.05). Conclusions: Patients who have performed the three cycles of hemotherapy demonstrated a susceptibility to the side effects of hematological toxicity (such as anemia and neutropenia); however, there was no relationship between ABCB1 and GSTP1 polymorphisms to hematological toxicity.

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The Role of ATP-Binding Cassette Transporters in the Chemoresistance of Anaplastic Thyroid Cancer: A Systematic Review

Endocrinology ◽

10.1210/en.2019-00241 ◽

2019 ◽

Vol 160 (8) ◽

pp. 2015-2023 ◽

Cited By ~ 4

Author(s):

Elnaz Abbasifarid ◽

Sayed Mahmoud Sajjadi-Jazi ◽

Maryam Beheshtian ◽

Hilda Samimi ◽

Bagher Larijani ◽

...

Keyword(s):

Systematic Review ◽

Thyroid Cancer ◽

Abc Transporters ◽

Anaplastic Thyroid Cancer ◽

Treatment Modalities ◽

Cochrane Library ◽

Atp Binding ◽

Resistance To Chemotherapy ◽

Atp Binding Cassette

AbstractAnaplastic thyroid cancer (ATC) is an aggressive type of thyroid cancer with a high mortality rate. Cytotoxic drugs are among the treatment modalities usually used for ATC treatment. However, systemic chemotherapies for ATC have not been shown to have remarkable efficacy. ATP-binding cassette (ABC) transporters have been suggested as a possible mechanism in ATC resistance to chemotherapy. This systematic review was aimed to define the possible roles of ABC transporters in ATC resistance to chemotherapy. Numerous databases, including Scopus, Web of Science, PubMed, Cochrane Library, Ovid, ProQuest, and EBSCO, were searched for papers published since 1990, with predefined keywords. The literature searches were updated twice, in 2015 and 2017. All identified articles were reviewed, and 14 papers that met the inclusion criteria were selected. In the eligible studies, the roles of 10 out of 49 ABC transporters were evaluated; among them, three pumps (ABCB1, ABCC1, and ABCG2) were the most studied transporters in ATC samples. ABCC1 and ABCG2 had the highest expression rates in ATC, and ABCB1 ranked second among the inspected transporters. In conclusion, ABC transporters are the major determinants of ATC resistance to chemotherapy. By identifying these transporters, we can tailor the best treatment approach for patients with ATC. Additional studies are needed to define the exact role of each ABC transporter and other mechanisms in ATC drug resistance.

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Impact of variants in ATP-binding cassette transporters on breast cancer treatment

Pharmacogenomics ◽

10.2217/pgs-2020-0106 ◽

2020 ◽

Vol 21 (18) ◽

pp. 1299-1310

Author(s):

Qingyang Xiao ◽

Yitian Zhou ◽

Volker M Lauschke

Keyword(s):

Breast Cancer ◽

Rare Variants ◽

Therapy Response ◽

Cancer Drug ◽

Atp Binding ◽

Breast Cancer Patients ◽

Cancer Drug Resistance ◽

The Impact ◽

Substantial Interest ◽

Atp Binding Cassette

There has been substantial interest in the impact of ATP-binding cassette (ABC) transporter variability on breast cancer drug resistance. Here, we provide a systematic review of ABC variants in breast cancer therapy. Notably, most studies used small heterogeneous cohorts and their identified associations lack statistical stringency, replication and mechanistic support. We conclude that commonly studied ABC polymorphisms are not suitable to accurately predict therapy response or toxicity in breast cancer patients and cannot guide treatment decisions. However, recent research shows that ABC transporters harbor a plethora of rare variants with individually small effect sizes, and we argue that a shift in strategy from target variant interrogation to comprehensive profiling might hold promise to drastically improve the predictive power of outcome models.

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Association of ATP-binding cassette sub-family B member 1 gene C3435T polymorphism with neutropenia in breast cancer patients treated with chemotherapy

Medical Journal of Indonesia ◽

10.13181/mji.v25i3.1326 ◽

2016 ◽

Vol 25 (3) ◽

pp. 156-62 ◽

Cited By ~ 2

Author(s):

Siti Syarifah ◽

Kamal B. Siregar ◽

Yahwardiah Siregar

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Absolute Neutrophil Count ◽

Neutrophil Count ◽

Common Adverse Event ◽

Wilcoxon Test ◽

Atp Binding ◽

Breast Cancer Patients ◽

C3435t Polymorphism ◽

Atp Binding Cassette

Background: Neutropenia is the most common adverse event of breast cancer chemotherapy which can be life threatening due to opportunistic infection, neutropenic episodes may lead to delay or reduction of drug doses which may compromise treatment outcomes. In this study, we investigated the association of ATP-binding cassette sub-family B member 1 (ABCB1) gene C3435T polymorphism with the grading of neutropenia in breast cancer patients who treated with doxorubicin-taxan.Methods: 72 Indonesian female breast cancer patients from Haji Adam Malik Hospital who had been diagnosed and treated with doxorubicin-taxane regimen were selected for this cohort study. DNA was extracted from peripheral leucocytes and ABCB1 C3435T polymorphism was analyzed with PCR-RFLP. Patient data were collected from patient’s medical record for 3 cycles of chemotherapy. Association between ABCB1 C3435T polymorphism with neutropenia was assessed using Kruskal-Wallis test. Decline of absolute neutrophil count was assessed using Wilcoxon test. Genotype deviation and allele frequencies were also determined by Hardy-Weinberg Equilibrium.Results: The frequencies of ABCB1 C3435T genotype for wildtype (CC), heterozygous (CT) and homozygous mutant (TT) was 22 (30.6%), 38 (52.8%) and 12 (16.7%) respectively. No association were found between ABCB1 C3435T polymorphism and the grading of neutropenia (p>0.05). There was a difference on the average of absolute neutrophil count after the first chemotherapy and after the third chemotherapy (p<0.05). There was no significant deviation of allele and genotype frequency from Hardy-Weinberg Equilibrium.Conclusion: ABCB1 C3435T polymorphism had no association with the grading of neutropenia in breast cancer patients treated with doxorubicin-taxane regimen, however there was a trend of absolute neutrophil count declining during the 3 cycles of chemotherapy.

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Assessment of Gene Expression Level of ATP Binding Cassette G Member 2 (ABCG2) Transporter in Newly Diagnosed Breast Cancer Patients Receiving Adjuvant Chemotherapy

Journal of Cancer Research Updates ◽

10.30683/1929-2279.2019.08.04 ◽

2019 ◽

Vol 8 ◽

pp. 22-28

Author(s):

Shaimaa Soliman ◽

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Gene Expression Level ◽

Expression Level ◽

Atp Binding ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Atp Binding Cassette

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Role of nanomedicine in reversing drug resistance mediated by ATP binding cassette transporters and P-glycoprotein in melanoma

Nanomedicine ◽

10.2217/nnm.11.48 ◽

2011 ◽

Vol 6 (4) ◽

pp. 701-714 ◽

Cited By ~ 6

Author(s):

Jagat R Kanwar ◽

Neha Singh ◽

Rupinder K Kanwar

Keyword(s):

Drug Resistance ◽

Atp Binding ◽

P Glycoprotein ◽

Atp Binding Cassette Transporters ◽

Atp Binding Cassette

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Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer

Frontiers in Pharmacology ◽

10.3389/fphar.2021.628690 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chao Dong ◽

Jiao Wu ◽

Yin Chen ◽

Jianyun Nie ◽

Ceshi Chen

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Progression ◽

Critical Role ◽

Acquired Resistance ◽

Mtor Inhibitors ◽

Disease Recurrence ◽

Mtor Pathway ◽

Breast Cancer Patients

Although chemotherapy, targeted therapy and endocrine therapy decrease rate of disease recurrence in most breast cancer patients, many patients exhibit acquired resistance. Hyperactivation of the PI3K/AKT/mTOR pathway is associated with drug resistance and cancer progression. Currently, a number of drugs targeting PI3K/AKT/mTOR are being investigated in clinical trials by combining them with standard therapies to overcome acquired resistance in breast cancer. In this review, we summarize the critical role of the PI3K/AKT/mTOR pathway in drug resistance, the development of PI3K/AKT/mTOR inhibitors, and strategies to overcome acquired resistance to standard therapies in breast cancer.

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