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T D, Mahalakshmi G, Mythili K, Srinivasa Rao K, Suresh Kumar S, Dubashi B, Shewade DG. Frequency Distributions of Alleles and Genotypes and Lung Cancer Risk of Polymorphisms DCK, SLC29A1, and SLC29A3 in South Indian Healthy Population. Cureus 2024; 16:e71896. [PMID: 39564037 PMCID: PMC11576072 DOI: 10.7759/cureus.71896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2024] [Indexed: 11/21/2024] Open
Abstract
Introduction Gemcitabine, a cytotoxic drug, is used to treat a variety of solid tumors, such as pancreatic, lung, and breast malignancies. The efficiency rates for gemcitabine have decreased due to an increase in genetic instability. The association between gene polymorphisms and the efficacy of gemcitabine therapy may be better known by understanding the intricacies of genetics that target a few or more genes in drug-targeting metabolic pathways. Moreover, several studies have documented differences in the therapeutic response among various ethnicities to gemcitabine chemotherapy. Therefore, the purpose of this study was to determine the normative frequencies of gene polymorphisms linked to the metabolic pathway of gemcitabine (DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776)) in Southern part of Indian healthy population and compared it with the 1000 genome population. In addition, the association of the above single nucleotide polymorphisms (SNPs) with lung cancer susceptibility was also evaluated. Methods The present study used real-time polymerase chain reaction (RT-PCR) for performing genotyping in 184 healthy participants as well as 123 South Indian patients with lung cancer. The frequencies of alleles and genotypes of the aforementioned genetic variants were in Hardy-Weinberg equilibrium (p > 0.05). Results The minor allele frequencies (MAF) of the SNPs DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1+913C>T (9394992), SLC29A3 +4967C>A (10999776) were 3.8%, 17.7%, 27.7%, 29.3% respectively in healthy population. The MAF of the SNPs, DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776) in lung cancer patients was 2%, 15%, 23.2%, and 24.4% respectively. A trend toward a protective effect against lung cancer was observed with SLC29A1 +913C>T (9394992). Conclusion The observed frequencies of alleles and genotypes in the South Indian population were significantly different as compared to the 1000 genome population. In the present study, an association of SLC29A1 rs9394992 C>T between lung cancer patients and healthy subjects showed a trend toward protective effect against lung cancer risk. There was no association found between the other studied SNPs and lung cancer risk.
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Affiliation(s)
- Devika T
- Department of Pharamcology, Guntur Medical College, Guntur, IND
| | | | - K Mythili
- Department of Physiology, Government Siddhartha Medical College, Vijayawada, IND
| | | | - Srinivasamurthy Suresh Kumar
- Department of Pharmacology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, ARE
| | - Biswajit Dubashi
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
| | - Deepak G Shewade
- Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
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Cao Y, Li PP, Qiao BL, Li QW. Kombo knife combined with sorafenib in liver cancer treatment: Efficacy and safety under immune function influence. World J Gastrointest Oncol 2024; 16:3118-3157. [PMID: 39072171 PMCID: PMC11271779 DOI: 10.4251/wjgo.v16.i7.3118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 01/02/2024] [Accepted: 03/20/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND In the quest to manage hepatocellular carcinoma (HCC), the focus has shifted to a more holistic approach encompassing both data analytics and innovative treatments. Analyzing rich data resources, such as the cancer genome atlas (TCGA), and examining progressive therapies can potentially reshape the trajectory of HCC treatment. AIM To elucidate the immunological genes and the underlying mechanism of the combined Kombo knife and sorafenib regimen for HCC by analyzing data from TCGA and machine learning data. METHODS Immune attributes were evaluated via TCGA's postablation HCC RNA sequencing data. Using weighted gene coexpression network analysis and machine learning, we identified genes with high prognostic value. The therapeutic landscape and safety metrics of the integrated treatment were critically evaluated across cellular and animal models. RESULTS Immune genes-specifically, peptidylprolyl isomerase A and solute carrier family 29 member 3-emerged as significant prognostic markers. Enhanced therapeutic outcomes, such as prolonged progression-free survival and an elevated overall response rate, characterize the combined approach, with peripheral blood mononuclear cells displaying potent effects on HCC dynamics. CONCLUSION The combination of Kombo knife with sorafenib is an innovative HCC treatment modality anchored in immune-centric strategies.
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Affiliation(s)
- Yang Cao
- Department of Oncology, The Third People's Hospital of Zhengzhou, Zhengzhou 450000, Henan Province, China
| | - Pei-Pei Li
- Department of Oncology, The Third People's Hospital of Zhengzhou, Zhengzhou 450000, Henan Province, China
| | - Bing-Li Qiao
- Department of Oncology, The Third People's Hospital of Zhengzhou, Zhengzhou 450000, Henan Province, China
| | - Quan-Wang Li
- Department of Oncology, The Affiliated Oriental Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
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Ma G, Rong Y, Liu SH, Guo H. SLC29A3 as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma. Asian J Surg 2024; 47:1936-1938. [PMID: 38233273 DOI: 10.1016/j.asjsur.2023.12.172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 12/25/2023] [Indexed: 01/19/2024] Open
Affiliation(s)
- Guorong Ma
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China
| | - Yao Rong
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Gansu, China
| | - Song-Hua Liu
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Gansu, China
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Ma H, Qu J, Liao Y, Liu L, Yan M, Wei Y, Xu W, Luo J, Dai Y, Pang Z, Qu Q. Equilibrative nucleotide transporter ENT3 (SLC29A3): A unique transporter for inherited disorders and cancers. Exp Cell Res 2024; 434:113892. [PMID: 38104646 DOI: 10.1016/j.yexcr.2023.113892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/07/2023] [Accepted: 12/12/2023] [Indexed: 12/19/2023]
Abstract
As a crucial gene associated with diseases, the SLC29A3 gene encodes the equilibrative nucleoside transporter 3 (ENT3). ENT3 plays an essential regulatory role in transporting intracellular hydrophilic nucleosides, nucleotides, hydrophilic anticancer and antiviral nucleoside drugs, energy metabolism, subcellular localization, protein stability, and signal transduction. The mutation and inactivation of SLC29A3 are intimately linked to the occurrence, development, and prognosis of various human tumors. Moreover, many hereditary human diseases, such as H syndrome, pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome, Faisalabad histiocytosis (FHC), are related to SLC29A3 mutations. This review explores the mechanisms of SLC29A3 mutations and expression alterations in inherited disorders and cancers. Additionally, we compile studies on the inhibition of ENT3, which may serve as an effective strategy to potentiate the anticancer activity of chemotherapy. Thus, the synopsis of genetics, permeant function and drug therapy of ENT3 provides a new theoretical and empirical foundation for the diagnosis, prognosis of evaluation and treatment of various related diseases.
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Affiliation(s)
- Hongying Ma
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Jian Qu
- Department of Pharmacy, The Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People's Republic of China; Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Yongkang Liao
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, People's Republic of China
| | - Linxin Liu
- Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Min Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Yiwen Wei
- Department of Pharmacy, The Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People's Republic of China
| | - Weixin Xu
- Department of Pharmacy, The Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People's Republic of China
| | - Jian Luo
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Yuxin Dai
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, People's Republic of China
| | - Zicheng Pang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Qiang Qu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410219, People's Republic of China.
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Song N, Pei Z, Fu G. MiR‐1224‐5p acts as a tumor suppressor via inhibiting the malignancy of rectal cancer through targeting SLC29A3. IUBMB Life 2020; 72:2204-2213. [DOI: 10.1002/iub.2352] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/05/2020] [Accepted: 07/07/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Na‐Sha Song
- Department of Thoracic Surgery Luoyang Central Affiliated to Zhengzhou university Luoyang P. R. China
| | - Zhi‐Dong Pei
- Department of Thoracic Surgery Luoyang Central Affiliated to Zhengzhou university Luoyang P. R. China
| | - Gui Fu
- Department of Thoracic Surgery Luoyang Central Affiliated to Zhengzhou university Luoyang P. R. China
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Yoshihama T, Fukunaga K, Hirasawa A, Nomura H, Akahane T, Kataoka F, Yamagami W, Aoki D, Mushiroda T. GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy: a comprehensive analysis using targeted resequencing of 100 pharmacogenes. Oncotarget 2018; 9:29789-29800. [PMID: 30038720 PMCID: PMC6049855 DOI: 10.18632/oncotarget.25712] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Accepted: 06/13/2018] [Indexed: 01/08/2023] Open
Abstract
Purpose To find genetic variants that predicted toxicity and/or efficacy of paclitaxel plus carboplatin combination therapy (TC therapy). Patients and methods In a retrospective case-control study, we analyzed 320 patients who had received TC therapy for gynecological cancers (ovarian, fallopian tube, peritoneal, uterine, and cervical cancers) and collected their germline DNA. We performed a comprehensive pharmacogenomic analysis using a targeted resequencing panel of 100 pharmacogenes. For 1,013 variants passing QC, case-control association studies and survival analyses were conducted. Results GSTP1 rs1695 showed the smallest p value for hematotoxicity association, and the 105Ile wild type allele had a significantly higher risk of severe hematotoxicity (neutropenia G4, thrombocytopenia ≥ G3 and anemia ≥ G3) than the 105Val allele (p=0.00034, odds ratio=5.71 (95% confidence interval:1.77-18.44)). Next, we assessed 5-year progression-free survival (PFS) and overall survival (OS) in 56 advanced ovarian cancer patients who received tri-weekly TC as a first-line chemotherapy. Patients with the 105Ile/105Ile genotype showed significantly better PFS (p=0.00070) and OS (p=0.0012) than those with the 105Ile/105Val or 105Val/105Val genotype. Conclusion Our study indicates that the GSTP1 rs1695 105Ile/105Ile genotype is associated with both severe hematotoxicity and high efficacy of TC therapy, identifying a possible prognostic indicator for patients with TC therapy.
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Affiliation(s)
- Tomoko Yoshihama
- Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.,Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Koya Fukunaga
- Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Akira Hirasawa
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Hiroyuki Nomura
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Tomoko Akahane
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Fumio Kataoka
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Wataru Yamagami
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Daisuke Aoki
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Taisei Mushiroda
- Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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SLC3A2 is upregulated in human osteosarcoma and promotes tumor growth through the PI3K/Akt signaling pathway. Oncol Rep 2017; 37:2575-2582. [PMID: 28350098 PMCID: PMC5428444 DOI: 10.3892/or.2017.5530] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 11/10/2016] [Indexed: 01/06/2023] Open
Abstract
Growing evidence indicates that SLC3A2 (solute carrier family 3 member 2) is upregulated and correlates with tumor growth in multiple types of cancers, while the role of SLC3A2 in human osteosarcoma (OS) is rarely discussed. Thus, the aim of the present study was to demonstrate the expression of SLC3A2 in human osteosarcoma and reveal its biological function and the underlying mechanisms. RT-PCR, western blot analysis and immunohistochemistry (IHC) were used to assess the expression of SLC3A2 in OS samples and cell lines. Cell cycle, Cell Counting Kit-8 (CCK-8) and colony formation assays were used to test the cell survival capacity. To investigate the potential mechanism by which SLC3A2 regulates OS growth, we used a slide-based antibody array. We demonstrated that SLC3A2 was upregulated in OS cell lines as well as OS tissues. High expression of SLC3A2 was correlated with clinical stage and tumor size in OS. Reduced expression of SLC3A2 inhibited OS cell proliferation through G2/M phase arrest. Most importantly, we found that SLC3A2 may regulate OS growth through the PI3K/Akt signaling pathway. In conclusion, SLC3A2 is upregulated in OS and plays a crucial role in tumor growth. Targeting SLC3A2 may provide a new therapeutic strategy for OS.
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Boswell-Casteel RC, Hays FA. Equilibrative nucleoside transporters-A review. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2016; 36:7-30. [PMID: 27759477 DOI: 10.1080/15257770.2016.1210805] [Citation(s) in RCA: 141] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. This review highlights findings on the characterization of ENTs by surveying studies on genetics, permeant and inhibitor interactions, mutagenesis, and structural models of ENT function.
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Affiliation(s)
- Rebba C Boswell-Casteel
- a Department of Biochemistry and Molecular Biology , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA
| | - Franklin A Hays
- a Department of Biochemistry and Molecular Biology , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA.,b Stephenson Cancer Center , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA.,c Harold Hamm Diabetes Center , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA
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Zaïr ZM, Singer DR. Influx transporter variants as predictors of cancer chemotherapy-induced toxicity: systematic review and meta-analysis. Pharmacogenomics 2016; 17:1189-1205. [PMID: 27380948 DOI: 10.2217/pgs-2015-0005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIM Chemotherapeutic agents have been shown to increase lung patient survival, however their use may be limited by their serious adverse effects. We aimed to assess int impact of pharmacogenetic variation of influx transporters on inter-individual patient variation in adverse drug reactions. PATIENTS & METHODS We conducted a meta-analysis and systemic review and identified 16 publications, totaling 1510 patients, to be eligible for review. RESULTS Meta-analysis showed east-Asian patients expressing SLCO1B1 521T>C or 1118G>A to have a two- to fourfold increased risk of irinotecan-induced neutropenia but not diarrhea. American patients, expressing SLC19A1 IVS2(4935) G>A, were further associated with pemetrexed/gemcitabine-induced grade 3+ leukopenia. CONCLUSION Future studies should look to robust validation of SLCO1B1 and SLC19A1 as prognostic markers in the management of lung cancer patients.
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Affiliation(s)
| | - Donald Rj Singer
- Yale University School of Medicine, New Haven, CT, USA.,Fellowship of Postgraduate Medicine 11 Chandos Street, London, UK
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Zaïr ZM, Singer DR. Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis. Pharmacogenomics 2016; 17:1089-112. [PMID: 27269636 DOI: 10.2217/pgs-2015-0006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
UNLABELLED Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). AIM With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. MATERIALS & METHODS Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. RESULTS Twenty-five publications comprising three randomised control trials, two retrospective case-controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for review. Of the known efflux drug transporters, we report findings on the ABC members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00-6.24; p = 0.05). CONCLUSION The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers.
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Affiliation(s)
| | - Donald Rj Singer
- Yale University School of Medicine, New Haven, CT 06510, USA.,Fellowship of Postgraduate Medicine, 11 Chandos Street, London, UK
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Lemstrová R, Souček P, Melichar B, Mohelnikova-Duchonova B. Role of solute carrier transporters in pancreatic cancer: a review. Pharmacogenomics 2014; 15:1133-45. [DOI: 10.2217/pgs.14.80] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Nucleoside analogs such as gemcitabine and 5-fluorouracil are currently the cornerstone of chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Decreased drug transport into tumor cells that may be caused by low expression of membrane proteins, such as solute carrier transporters, represents one of the principal mechanisms of chemotherapy resistance. Individual diversity of multidrug resistance is the major challenge limiting the success of anticancer treatment. Novel biomarkers and pharmacogenomic approaches could further optimize treatment algorithms leading to better survival and lower treatment toxicity in PDAC patients. In this review, the most promising predictive biomarkers from the solute carrier transporter family of membrane transporters and the potential applications for PDAC therapy with nucleoside analogues are summarized.
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Affiliation(s)
- Radmila Lemstrová
- Department of Oncology, Palacky University Medical School & Teaching Hospital, Olomouc, Czech Republic
| | - Pavel Souček
- Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic
| | - Bohuslav Melichar
- Department of Oncology, Palacky University Medical School & Teaching Hospital, Olomouc, Czech Republic
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