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Review

Pharmacogenetics in the treatment of gastrointestinal stromal tumors – an updated review

ORCID Icon, , ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 797-808 | Received 31 Mar 2020, Accepted 26 Jun 2020, Published online: 12 Jul 2020

References

  • Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004;22:3813–3825.
  • Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480.
  • Mazzocca A, Napolitano A, Silletta M, et al. New frontiers in the medical management of gastrointestinal stromal tumours. Ther Adv Med Oncol. 2019;11:175883591984194. SAGE Publications Inc.
  • Evans EK, Gardino AK, Kim JL, et al. A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med. 2017;9(414):eaao1690.
  • Avapritinib Approved for GIST Subgroup. Cancer Discov. 2020 Mar;10(3):334. DOI: 10.1158/2159-8290.CD-NB2020-003
  • von Mehren M, Randall R, Benjamin R, et al. Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16:536–563.
  • Ravegnini G, Hrelia P, Angelini S. Somatic pharmacogenomics of gastrointestinal stromal tumor. Cancer Drug Resist. 2019. DOI:10.20517/cdr.2019.02
  • Casali PG, Abecassis N, Bauer S, et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2018 Oct 1;29(Suppl 4):iv267.DOI: 10.1093/annonc/mdy320
  • Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–4349.
  • Heinrich MC, Maki RG, Corless CL, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008;26:5352–5359.
  • Hertz DL, McLeod HL. Use of pharmacogenetics for predicting cancer prognosis and treatment exposure, response and toxicity. J Hum Genet. 2013;58:346–352.
  • Ravegnini G, Sammarini G, Serrano C, et al. Clinical relevance of circulating molecules in cancer: focus on gastrointestinal stromal tumors. Ther Adv Med Oncol. 2019;11:1758835919831902.
  • Ravegnini G, Nannini M, Sammarini G, et al. Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): clinical Implications of the Somatic and Germline DNA Analysis. Int J Mol Sci. 2015;16:15592–15608.
  • Ravegnini G, Sammarini G, Angelini S, et al. Pharmacogenetics of tyrosine kinase inhibitors in gastrointestinal stromal tumor and chronic myeloid leukemia. Expert Opin Drug Metab Toxicol. 2016;12:733–742.
  • Liu JJ, Ward RL. Folate and one-carbon metabolism and its impact on aberrant DNA methylation in cancer. Adv Genet. 2010;71:79–121.
  • Okamoto Y, Sawaki A, Ito S, et al. Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumour. Gut. 2012;61:392–401.
  • Touzart A, Boissel N, Belhocine M, et al. Low level CpG island promoter methylation predicts a poor outcome in adult T-cell acute lymphoblastic leukemia. Haematologica. 2020 Jun;105(6):1575-1581. .DOI: 10.3324/haematol.2019.223677.
  • Wang Z, Deng T, Long X, et al. Methylation of SRD5A2 promoter predicts a better outcome for castration-resistant prostate cancer patients undergoing androgen deprivation therapy. PLoS One. 2020;15:e0229754. Saleem M, editor.
  • Peng Y, Wu Q, Wang L, et al. A DNA methylation signature to improve survival prediction of gastric cancer. Clin Epigenetics. 2020;12. DOI:10.1186/s13148-020-0807-x.
  • Bertino JR, Banerjee D, Mishra PJ. Pharmacogenomics of microRNA: A miRSNP towards individualized therapy. Pharmacogenomics. 2007;8:1625–1627.
  • Mishra PJ, Banerjee D, Bertino JR. MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: introducing microRNA pharmacogenomics. Cell Cycle. 2008;7:853–858. Taylor and Francis Inc.
  • Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138:103–141.
  • Cipollini M, Landi S, Gemignani F. MicroRNA binding site polymorphisms as biomarkers in cancer management and research. Pharmgenomics Pers Med. 2014;7:173–191.
  • Dzikiewicz-Krawczyk A. MicroRNA polymorphisms as markers of risk, prognosis and treatment response in hematological malignancies. Crit Rev Oncol Hematol. 2015;93:1–17.
  • Ravegnini G, Serrano C, Simeon V, et al. The rs17084733 variant in the KIT 3’ UTR disrupts a miR-221/222 binding site in gastrointestinal stromal tumour: a sponge-like mechanism conferring disease susceptibility. Epigenetics. 2019;14:545–557. In Press.
  • Du Y, Lin Y, Yin K, et al. Single nucleotide polymorphisms of let-7-related genes increase susceptibility to breast cancer. Am J Transl Res. 2019;11:1748–1759.
  • Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011;11:865–878.
  • Angelini S, Pantaleo MA, Ravegnini G, et al. Polymorphisms in OCTN1 and OCTN2 transporters genes are associated with prolonged time to progression in unresectable gastrointestinal stromal tumours treated with imatinib therapy. Pharmacol Res. 2013;68:1–6.
  • Koo D-H, Ryu M-H, Ryoo B-Y, et al. Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor. Cancer Chemother Pharmacol. 2015;75:173–182.
  • Brahmi M, Alberti L, Dufresne A, et al. KIT exon 10 variant (c.1621 A > C) single nucleotide polymorphism as predictor of GIST patient outcome. BMC Cancer. 2015;15:780.
  • Angelini S, Ravegnini G, Nannini M, et al. Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome. Eur J Hum Genet. 2015;23:817–823.
  • Ravegnini G, Nannini M, Simeon V, et al. Polymorphisms in DNA repair genes in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome. Tumour Biol. 2016;37(10):13413–13423.
  • Cao X, Zhou Y, Sun H, et al. EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790 M resistant mutation in lung cancer cells. Cancer Lett. 2018;424:84–96.
  • Kiwerska K, Szyfter K. DNA repair in cancer initiation, progression, and therapy-a double-edged sword. J Appl Genet. 2019;60:329–334.
  • Ghiringhelli F, Richard C, Chevrier S, et al. Efficiency of olaparib in colorectal cancer patients with an alteration of the homologous repair protein. World J Gastroenterol. 2016;22:10680–10686.
  • Klinakis A, Karagiannis D, Rampias T. Targeting DNA repair in cancer: current state and novel approaches. Cell Mol Life Sci. 2020;77:677–703.
  • Verboom MC, Kloth JSL, Swen JJ, et al. Genetic polymorphisms in angiogenesis-related genes are associated with worse progression-free survival of patients with advanced gastrointestinal stromal tumours treated with imatinib. Eur J Cancer. 2017;86:226–232.
  • Glubb DM, Cerri E, Giese A, et al. Novel functional germline variants in the VEGF receptor 2 gene and their effect on gene expression and microvessel density in lung cancer. Clin Cancer Res. 2011;17:5257–5267.
  • Wasielewski K, Wasag B, Wozniak A, et al. Influence of cytochrome P450, ABC and SLC gene polymorphisms on imatinib therapy outcome of patients with gastrointestinal stromal tumours (GIST). Folia Biol (Czech Republic). 2017;63:78–83.
  • Ravegnini G, Urbini M, Simeon V, et al., An exploratory study by DMET array identifies a germline signature associated with imatinib response in gastrointestinal stromal tumor. Pharmacogenomics J. 2019;19(4): 390–400.
  • Chen F, Liu Y, Wang S, et al. Triptolide, a Chinese herbal extract, enhances drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2. Pharmacogenomics. 2013;14:1305–1317.
  • Xu L, Zhao Y, Pan F, et al. Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments. Biomed Res Int. 2019;2019:6502793.
  • Xie Q, Lin Q, Li D, et al. Imatinib induces autophagy via upregulating XIAP in GIST882 cells. Biochem Biophys Res Commun. 2017;488:584–589.
  • Liu L, Zhou J, Wang Y, et al. Imatinib inhibits oxidative stress response in spinal cord injury rats by activating Nrf2/HO‑1 signaling pathway. Exp Ther Med. 2019;19:597–602.
  • Ma D, Fang Q, Wang P, et al. Induction of Heme Oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in Imatinib-resistant chronic myeloid leukemia cells. J Biol Chem. 2015;290:12558–12571.
  • Synowiec E, Hoser G, Wojcik K, et al. UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib. Int J Mol Sci. 2015;16:18111–18128.
  • Kim T-W, Kim Y-J, Kim H-T, et al. NQO1 Deficiency Leads Enhanced Autophagy in Cisplatin-Induced Acute Kidney Injury Through the AMPK/TSC2/mTOR Signaling Pathway. Antioxid Redox Signal. 2016;24:867–883.
  • Ravegnini G, Sammarini G, Nannini M, et al. Gastrointestinal stromal tumors (GIST): facing cell death between autophagy and apoptosis. Autophagy. 2017;13:452–463.
  • Mihajlovic M, Ivkovic B, Jancic-Stojanovic B, et al. Modulation of oxidative stress/antioxidative defence in human serum treated by four different tyrosine kinase inhibitors. Anticancer Drugs. 2020;Publish Ahead of Print. DOI:10.1097/CAD.0000000000000924.
  • Frias DP, Gomes RLN, Yoshizaki K, et al. Nrf2 positively regulates autophagy antioxidant response in human bronchial epithelial cells exposed to diesel exhaust particles. Sci Rep. 2020;10:3704.
  • Song S, Lee JY, Ermolenko L, et al. Tetrahydrobenzimidazole TMQ0153 triggers apoptosis, autophagy and necroptosis crosstalk in chronic myeloid leukemia. Cell Death Dis. 2020;11. DOI:10.1038/s41419-020-2304-8.
  • van Oosterom AT, Judson IR, Verweij J, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2002;38(Suppl 5):S83–7.
  • DeMatteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:1097–1104.
  • Aliberti S, Grignani G, Allione P, et al. An acute hepatitis resembling autoimmune hepatitis occurring during imatinib therapy in a gastrointestinal stromal tumor patient. Am J Clin Oncol. 2009;32:640–641.
  • Tonyali O, Coskun U, Yildiz R, et al. Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors. Med Oncol. 2010;27:768–773.
  • Yachoui R. Early onset imatinib mesylate-induced hepatotoxicity in a patient with gastrointestinal stromal tumors. Am J Ther. 2014;21:e148–50.
  • Haq MI, Nixon J, Stanley AJ. Imatinib and liver toxicity. BMJ Case Rep. 2018;11:e226740.
  • Saif MW, Smith MH, Maloney A, et al. Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism: first case series in patients with gastrointestinal stromal tumor. Ann Gastroenterol. 2016;29:551–556.
  • Miners JO, McKinnon RA, Mackenzie PI. Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology. 2002;181–182:453–456.
  • Chen SPL, Poon WT, Mak CM, et al. Application of pharmacogenetics: UGT1A1*28 and nilotinib-induced unconjugated hyperbilirubinaemia in a patient with chronic myeloid leukaemia. Pathology. 2011;43:273–274. Lippincott Williams and Wilkins.
  • Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A. 1998;95:8170–8174.
  • Singer JB, Shou Y, Giles F, et al. UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia. 2007;21:2311–2315.
  • Abumiya M, Takahashi N, Niioka T, et al. Influence of UGT1A1 *6, *27, and *28 polymorphisms on nilotinib-induced hyperbilirubinemia in Japanese patients with chronic myeloid leukemia. Drug Metab Pharmacokinet. 2014;29:449–454.
  • Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013;36:491–503.
  • Falvella FS, Cheli S, Martinetti A, et al. DPD and UGT1A1 deficiency in colorectal cancer patients receiving triplet chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan. Br J Clin Pharmacol. 2015;80:581–588.
  • Teo YL, Ho HK, Chan A. Formation of reactive metabolites and management of tyrosine kinase inhibitor-induced hepatotoxicity: a literature review. Expert Opin Drug Metab Toxicol. 2015;11:231–242.
  • Carretero-González A, Salamanca Santamaría J, Castellano D, et al. Three case reports: temporal association between tyrosine-kinase inhibitor-induced hepatitis and immune checkpoint inhibitors in renal cell carcinoma. Medicine (Baltimore). 2019;98:e18098.
  • Qian J, Zhang X, Zhang B, et al. Hepatotoxicity in advanced lung adenocarcinoma: A retrospective study of 2108 cases. J Cancer. 2018;9:1607–1613.
  • Qosa H, Avaritt BR, Hartman NR, et al. In vitro UGT1A1 inhibition by tyrosine kinase inhibitors and association with drug-induced hyperbilirubinemia. Cancer Chemother Pharmacol. 2018;82:795–802.
  • Liu J, Chen Z, Chen H, et al. Genetic polymorphisms contribute to the individual variations of imatinib mesylate plasma levels and adverse reactions in Chinese GIST patients. Int J Mol Sci. 2017 Mar 13;18(3):603. DOI: 10.3390/ijms18030603
  • Burk O, Arnold KA, Nussler AK, et al. Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005;67:1954–1965.
  • Albermann N, Schmitz-Winnenthal FH, Z’graggen K, et al. Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver. Biochem Pharmacol. 2005;70:949–958.
  • Cerveny L, Svecova L, Anzenbacherova E, et al. Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metab Dispos. 2007;35:1032–1041.
  • Qiu H-B, Zhuang W, Wu T, et al. Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1. Pharmacogenomics J. 2018;18:460–466.
  • Zhang Q, Xu J, Qian Y, et al. Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors. Mol Cancer Ther. 2018;17:2780–2787.
  • Chen H, Liu J, Zhou Y, et al. Association of Hepatic Nuclear Factor 4 Alpha Gene Polymorphisms With Free Imatinib Plasma Levels and Adverse Reactions in Chinese Gastrointestinal Stromal Tumor Patients. Ther Drug Monit. 2019;41:582–590.
  • Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression. Pharmacol Rev. 2002;54:129–158.
  • Kamiyama Y, Matsubara T, Yoshinari K, et al. Role of human hepatocyte nuclear factor 4alpha in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet. 2007;22:287–298.
  • Hwang-Verslues WW, Sladek FM. HNF4α–role in drug metabolism and potential drug target? Curr Opin Pharmacol. 2010;10:698–705.
  • Kloth JSL, Verboom MC, Swen JJ, et al. Genetic polymorphisms as predictive biomarker of survival in patients with gastrointestinal stromal tumors treated with sunitinib. Pharmacogenomics J. 2018;18:49–55.
  • Qian Y, Sun LN, Liu YJ, et al. Genetic polymorphisms and adverse events on unbound imatinib and its active metabolite concentration in patients with gastrointestinal stromal tumors. Front Pharmacol. 2019;10. DOI:10.3389/fphar.2019.00854.
  • Rutkowski P, Bylina E, Klimczak A, et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study. BMC Cancer. 2012;12:107.
  • Ravegnini G, Nannini M, Zenesini C, et al. An exploratory association of polymorphisms in angiogenesis-related genes with susceptibility, clinical response and toxicity in gastrointestinal stromal tumors receiving sunitinib after imatinib failure. Angiogenesis. 2017;20:139–148.
  • Kim JJ, Vaziri SAJ, Rini BI, et al. Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib. Cancer. 2012;118:1946–1954.
  • Giampieri R, Salvatore L, Del Prete M, et al. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. Sci Rep. 2016;6:25195.
  • Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.
  • De Mattia E, Cecchin E, Guardascione M, et al. Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma. World J Gastroenterol. 2019;25:3870–3896. Baishideng Publishing Group Co., Limited.
  • Suenaga M, Schirripa M, Cao S, et al. Gene Polymorphisms in the CCL5/CCR5 Pathway as a Genetic Biomarker for Outcome and Hand-Foot Skin Reaction in Metastatic Colorectal Cancer Patients Treated With Regorafenib. Clin Colorectal Cancer. 2018;17:e395–e414.
  • Blay J-Y, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jun 5;S1470-2045(20)30168-6.DOI: 10.1016/S1470-2045(20)30168-6
  • Duffaud F, Blay J-Y. Gastrointestinal Stromal Tumors: biology and Treatment. Oncology. 2003;65:187–197.
  • Prasad V, Fojo T, Brada M. Precision oncology: origins, optimism, and potential. Lancet Oncol. 2016;17:e81–e86.
  • Liang Z, Huang JX, Zeng X, et al. DL-ADR: A novel deep learning model for classifying genomic variants into adverse drug reactions. BMC Med Genomics. 2016;9:48.
  • Valdés MG, Galván-Femenía I, Ripoll VR, et al. Pipeline design to identify key features and classify the chemotherapy response on lung cancer patients using large-scale genetic data. BMC Syst Biol. 2018;12:97.
  • Lopez C, Tucker S, Salameh T, et al. An unsupervised machine learning method for discovering patient clusters based on genetic signatures. J Biomed Inform. 2018;85:30–39.
  • Xie X, Hanson C, Sinha S. Mechanistic interpretation of non-coding variants for discovering transcriptional regulators of drug response. BMC Biol. 2019;17:62.
  • Nannini M, Ravegnini G, Angelini S, et al. miRNA profiling in gastrointestinal stromal tumors: implication as diagnostic and prognostic markers. Epigenomics. 2015;7:1033–1049.
  • Mei L, Smith SC, Faber AC, et al. Gastrointestinal Stromal Tumors: the GIST of Precision Medicine. Trends Cancer. 2018;4:74–91.

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