Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.
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http://dx.doi.org/10.1038/tpj.2016.38 | DOI Listing |
Eur J Pharm Sci
January 2025
Centre for Applied Pharmacokinetic Research, University of Manchester, UK.
Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.
View Article and Find Full Text PDFInvest New Drugs
January 2025
Dipartimento Di Ricerca Traslazionale E Delle Nuove Tecnologie in Medicina E Chirurgia, Università Di Pisa, Via Savi 10, 56126, Pisa, Italy.
Cutaneous T-cell lymphomas (CTCLs) are a rare and heterogeneous subset of skin-localized, non-Hodgkin lymphomas. Our aim was to evaluate the in vitro antitumor activity of the multi-kinase inhibitor linifanib, either alone or in combination with metronomic vinorelbine (mVNR) or etoposide (mETO), on CTCL cells. In vitro proliferation assay and Luminex analysis showed that long-term, daily exposure of linifanib significantly inhibited the proliferation of the human CTCL cell line HH, in a concentration-dependent manner (IC = 48.
View Article and Find Full Text PDFBMC Cancer
January 2025
School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, 261053, P.R. China.
Background: ABCB1 overexpression is a key factor in causing multidrug resistance (MDR). As a result, it is crucial to discover effective medications against ABCB1 to overcome MDR. Falnidamol, a tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), is currently in phase 1 clinical trials for the treatment of solid tumors.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Breast cancer is a leading cause of cancer-related deaths among women globally. It is imperative to explore novel biomarkers to predict breast cancer treatment response as well as progression. Here, we collected six breast cancer samples and paired normal tissues for high-throughput sequencing.
View Article and Find Full Text PDFEur J Pharmacol
February 2025
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei, 10507, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address:
Multidrug resistance (MDR) remains a significant obstacle in cancer treatment, primarily attributable to the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2 within cancer cells. These transporters actively diminish the effectiveness of cytotoxic drugs by facilitating ATP hydrolysis-dependent drug efflux, thereby reducing intracellular drug accumulation. Given the absence of approved treatments for multidrug-resistant cancers and the established benefits of combining tyrosine kinase inhibitors (TKIs) with conventional anticancer drugs, we investigate the potential of vodobatinib, a potent c-Abl TKI presently in clinical trials, to restore sensitivity to chemotherapeutic agents in multidrug-resistant cancer cells overexpressing ABCB1 and ABCG2.
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