Pharmacogenetics and Personalized Medicine in Pancreatic Cancer
Pancreatic cancer (PC) is a progressive, fatal disease with a high degree of malignancy. More than 40000 peoplediefrom this cancer annually in the United States. As a multifactorial condition, PC has a complex nature, and there are several genes and signalingpathwaysimplicated in PC pathogenesis and progression. There are diffèrent mutations in master genesincludingtumorsuppressors and oncogenesthat lead to Pancreaticintraepithelialneoplasia (PanIN) whichis the mostcommon non-invasive precursorlesion of pancreatic cancer. These mutations influence directly or indirectly the cycle of Pharmacodynamics profile. Interactions between genetics and drug metabolism could be considered as one of the most important insights in the personalized medicine and targeted therapy based on the genetic profile of each affected person. In this literature, we will discuss pathogenesis and susceptibility to PC, pharmacogenetics and personalized medicine in pancreatic cancer and scrutinized the most important genes, variations and signaling pathways that influence individualized therapy of PC.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. (Accessed December 2016, 30, at http://onlinelibrary.wiley.com/doi/10.3322/caac.21332/ful l).
Timmermann B, Kerick M, Roehr C, Fischer A, Isau M, Boerno ST, et al. Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis.PloSOne 2010;5:e15661.
Roberts NJ, Norris AL, Petersen GM, Bondy ML, Brand R, Gallinger S, et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov 2016;6:166-175.
Lennon AM, Wolfgang CL, Canto MI, Klein AP, Herman JM, Goggins M, et al. The early detection of pancreatic
cancer: what will it take to diagnose and treat curable pancreatic neoplasia? Cancer Res 2014;74:3381-9.
Cowan RW, Maitra A. Genetic progression of pancreatic cancer. Cancer J2014;20:80-4.
Delpu Y, Hanoun N, Lulka H, Sicard F, Selves J,BuscailL,et al. Genetic and epigenetic alterations in pancreatic carcinogenesis.CurrGenomics 2011;12:15-54.
Eser S, Schnieke A, Schneider G, Saur D. Oncogenic KRAS signalling in pancreatic cancer. Br JCancer 2014;111:817-22.
Taniguchi C, Maitra A. It’sa SMAD/SMAD World. Cell 2015;161:1245-6.
Weissmueller S, Manchado E, Saborowski M, Morris JP 4th, Wagenblast E, Davis CA, et al. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling. Cell 2014;157:382-94.
Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015;518:495-501.
Olson SH, Kurtz RC. Epidemiology of pancreatic cancer and the role of family history. JSurgOncol 2013;107:1-7.
Korsse SE, Harinck F, van Lier MG, Biermann K, Offerhaus GJ, Krak N, et al. Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance. J Med Genet 2013;50:59-64.
Gukovsky I, Li N, Todoric J, Gukovskaya A, Karin M.Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology 2013;144:1199-209.
Steinke V, Engel C, Büttner R, Schackert HK, Schmiegel WH, Propping P. Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. DtschArzteblInt 2013;110:32-8.
Grant RC, Selander I, Connor AA, Selvarajah S, Borgida A, Briollais L, et al. Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology 2015;148:556-64.
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363:1049-57.
Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. AnnSurg 2015;261:12-7.
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. NEnglJ Med2013;369:1691-703.
Wang M, Tang W, Xin H, Zhu YZ. S-Propargyl- Cysteine, a Novel Hydrogen Sulfide Donor, Inhibits
Inflammatory Hepcidin and Relieves Anemia of Inflammation by Inhibiting IL-6/STAT3 Pathway. PloSOne 2016;11:e0163289.
Kan J, Guo W, Huang C, Bao G, Zhu Y, Zhu YZ. S- propargyl-cysteine, a novel water-soluble modulator of endogenous hydrogen sulfide, promotes angiogenesis through activation of signal transducer and activator of transcription 3. Antioxid Redox Signal 2014;2:2303-16.
Gharaibeh M, McBride A, Bootman JL, Patel H, Abraham I. Economic evaluation for the US of nab- paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer. J Med Econ 2016:1-8.
Hosseini Bereshneh A, Soltani D, Veisi N, Khademi M, Modarressi MH. Horizons of personalized medicine in breast cancer treatment. TUMJ 2016;74. [Epub ahead of print]
Ferrer-Lorenzo E, Nussbaum DP, Winter P, Wood K.Systematic interrogation of druggable pathways in pancreatic adenocarcinomas using pooled gene- knockdown lentiviral libraries. Cancer Res 2015;75:5465.
Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology 2014;28:39-48.
Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, et al. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 2014;158:929-44.
Neoptolemos JP, Cox TF, Greenhalf W, Garner L, Campbell F, Ghaneh P, et al. High hENT1 expression is predictive of response of to adjuvant gemcitabine for pancreatic ductal adenocarcinoma patients randomized to adjuvant therapies in the ESPAC trials. Pancreatology2013;13:e6.
Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Actaoncologica 2015;54:979-85.
Toyota Y, Iwama H, Kato K, Tani J, Katsura A, Miyata M, et al. Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth. Int J Oncol 2015;47:1293-302.
Adhikary A, Kumar A, Rayala R, Hindi RM, Adhikary A, Wnuk SF, et al. One-Electron Oxidation of Gemcitabine and Analogs: Mechanism of Formation of C3′ and C2′Sugar Radicals. J Am ChemSoc 2014;136:15646-53.
Shirkoohi R, Azimi C. Neoplasia from genetic point of view. Acta Med Iran 2013;51:663-74.
Tourkantonis IS, Peponi E, Syrigos KN, Saif MW. "Pharmacogenetics in Pancreatic Cancer. JOP
Lemstrová, Radmila, Souček P, Melichar B, Mohelnikova-Duchonova B. Role of solute carrier transporters in pancreatic cancer: a review. Pharmacogenomics 2014;15:1133-45.
Estudante M, Soveral G, Moris JG, Benet LZ. Insights into solute carriers: physiological functions and implications in disease and pharmacokinetics. Med Chem Comm 2016;7:1462-78.
MuengsaenD, Vannaprasaht S, Tassaneeyakul W, Butthongkomvong K, Bowornkitiwong T, Thongthieang L, et al. The Effect of CytidineDeaminase Polymorphisms on Hematotoxicity in Thai Cancer Patients Treated with Gemcitabine-based Chemotherapy. Srinagarind Med J2016;31:105-8.
Roseberry Baker JA, Wickremsinhe E, Li CH, Guo Y.Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidinedeaminase and deoxycytidine kinase. Drug Metab Dispos 2013;41:541-5.
Weizman N, Krelin Y, Shabtay-Orbach A, Amit M, Binenbaum Y, Wong RJ, Gil Z. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulatingcytidinedeaminase. Oncogene 2014;33:3812-9.
Patzak M, Hessmann E, Bapiro TE, Neesse A.Gemcitabine uptake and metabolism of cancer associated fibroblasts in murine pancreatic cancer. Z Gastroenterol 2016;54:KV466.
de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 2014;741:8-16.
Helleday T. Poisoning Cancer Cells with Oxidized Nucleosides. NEngl J Med 2015;373:1570-1.
Alvarellos ML, Lamba J, Sangkuhl K, Thorn CF, Wang L, Klein DJ, et al. PharmGKB summary: gemcitabine pathway. Pharmacogenet Genomics 2014;24:564-74.
Lüske C. Molecular determinants for the outcome in gemcitabine-treated pancreatic cancer [dissertation]. Diss Georg-August University Göttingen, 2015.
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