title: Polymorphisms of Genes Encoding Multidrug Resistance Proteins as a Predictive Factor for Second-Line Docetaxel Therapy in Advanced Non-small Cell Lung Cancer.
abstract: Multidrug resistance (MDR) remains a substantial problem in chemotherapy. The purpose of the study was to investigate potential factors, including MDR genes polymorphisms, that could be used in qualification for second-line docetaxel therapy in non-small cell lung cancer (NSCLC) patients after failure of platinum based chemotherapy. Study group comprised of 58 Caucasian subjects. Evaluation of Single Nucleotide Polymorphisms (SNPs) of ABCC2/MRP2 and ABCB1/MDR1 genes was performed using the High Resolution Melting (HRM) technique. TUBB3 gene expression was evaluated on RNA isolated from tumor tissue. Results with p value of <0.05 were considered significant. Factors associated with reduced risk of disease progression included good performance status (PS), long period between diagnosis and docetaxel treatment, and smoking for <10 pack-years. Disease control occurred more often in patients with G/G genotype of the ABCC2/MRP2 gene. Median overall survival was 4.25 months. Factors such as: good PS, disease control after docetaxel, long period from diagnosis to docetaxel, lack of significant weight loss, and third-line treatment were associated with prolongation of patients survival. Overall survival probability was significantly lower in patients with significant weight loss, poor PS, lack of disease control after docetaxel, and without third-line treatment. Factors that characterized the highest risk of survival shortening were: inability to apply third-line treatment, lack of best response to first-line therapy, poor PS, and C/G or G/G genotypes of ABCC2/MRP2 gene. We concluded that assessed factors had mainly prognostic and not predictive value. Finding reliable molecular predictors for second line docetaxel therapy requires further clinical trials.
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland. mszczyrek@yahoo.co.uk.|Chair of Internal Medicine and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland. mszczyrek@yahoo.co.uk.
authors.forename: Michał
authors.initials: M
authors.lastname: Szczyrek
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Radosław
authors.initials: R
authors.lastname: Mlak
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Wojas-Krawczyk
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Powrózek
authors.affiliation: Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Szudy-Szczyrek
authors.affiliation: Chair of Internal Medicine and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zwolak
authors.affiliation: Chair of Internal Medicine and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Daniluk
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D018450:Disease Progression; D000077143:Docetaxel; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D043823:Taxoids / Q000627:therapeutic use*; D014404:Tubulin / Q000235:genetics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000077143:Docetaxel; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D043823:Taxoids; D014404:Tubulin; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human
keywords: ABCC2; Docetaxel; MDR1; NSCLC; TUBB3