Top

Published in:

01-02-2018 | Review Article

Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma

Authors: Kazuhiro Yamamoto, Ikuko Yano

Published in: Medical Oncology | Issue 2/2018

Abstract

The prognosis of patients with metastatic renal cell carcinoma has drastically improved due to the development of molecular-targeted drugs and their use in clinical practice. However, these drugs cause some diverse adverse reactions in patients and sometimes affect clinical outcomes of cancer therapy. Therefore, predictive markers are necessary to avoid severe adverse reactions, to establish novel and effective prevention methods, and to improve treatment outcomes. Some genetic factors involved in these adverse reactions have been reported; however, perspectives on each adverse response have not been integrated yet. In this review, genetic polymorphisms relating to molecular-targeted therapy-induced adverse reactions in patients with renal cell carcinoma are summarized in the points of pharmacokinetic and pharmacodynamic mechanisms. We also discuss about the relationship between systemic drug exposure and adverse drug reactions.

Barata PC, Rini BI. Treatment of renal cell carcinoma: current status and future directions. CA Cancer J Clin. 2017;67(6):507–24. https://doi.org/10.3322/caac.21411.CrossRefPubMed

Sanchez-Gastaldo A, Kempf E, Gonzalez Del Alba A, Duran I. Systemic treatment of renal cell cancer: a comprehensive review. Cancer Treat Rev. 2017;60:77–89. https://doi.org/10.1016/j.ctrv.2017.08.010.CrossRefPubMed

Li Y, Gao ZH, Qu XJ. The adverse effects of sorafenib in patients with advanced cancers. Basic Clin Pharmacol Toxicol. 2015;116(3):216–21. https://doi.org/10.1111/bcpt.12365.CrossRefPubMed

Frampton JE. Pazopanib: a review in advanced renal cell carcinoma. Targeted Oncol. 2017;12(4):543–54. https://doi.org/10.1007/s11523-017-0511-8.CrossRef

Cohen RB, Oudard S. Antiangiogenic therapy for advanced renal cell carcinoma: management of treatment-related toxicities. Invest New Drugs. 2012;30(5):2066–79. https://doi.org/10.1007/s10637-012-9796-8.CrossRefPubMedPubMedCentral

Josephs DH, Fisher DS, Spicer J, Flanagan RJ. Clinical pharmacokinetics of tyrosine kinase inhibitors: implications for therapeutic drug monitoring. Ther Drug Monit. 2013;35(5):562–87. https://doi.org/10.1097/FTD.0b013e318292b931.PubMed

Neul C, Schaeffeler E, Sparreboom A, Laufer S, Schwab M, Nies AT. Impact of membrane drug transporters on resistance to small-molecule tyrosine kinase inhibitors. Trends Pharmacol Sci. 2016;37(11):904–32. https://doi.org/10.1016/j.tips.2016.08.003.CrossRefPubMed

Vaziri SA, Kim J, Ganapathi MK, Ganapathi R. Vascular endothelial growth factor polymorphisms: role in response and toxicity of tyrosine kinase inhibitors. Current Oncol Rep. 2010;12(2):102–8. https://doi.org/10.1007/s11912-010-0085-4.CrossRef

Song M. Recent developments in small molecule therapies for renal cell carcinoma. Eur J Med Chem. 2017. https://doi.org/10.1016/j.ejmech.2017.08.007.

10.

Subramanian P, Haas Md NB. Recent advances in localized RCC: a focus on VEGF and immuno-oncology therapies. Urol Oncol. 2017. https://doi.org/10.1016/j.urolonc.2017.09.008.PubMed

11.

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. New Engl J Med. 2007;356(2):125–34. https://doi.org/10.1056/NEJMoa060655.CrossRefPubMed

12.

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–90. https://doi.org/10.1200/jco.2008.20.1293.CrossRefPubMedPubMedCentral

13.

Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14(13):1287–94. https://doi.org/10.1016/s1470-2045(13)70465-0.CrossRefPubMed

14.

Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in Locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8. https://doi.org/10.1200/jco.2009.23.9764.CrossRefPubMed

15.

Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet (Lond, Engl). 2008;372(9637):449–56. https://doi.org/10.1016/s0140-6736(08)61039-9.CrossRef

16.

Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. New Engl J Med. 2007;356(22):2271–81. https://doi.org/10.1056/NEJMoa066838.CrossRefPubMed

17.

Lee SH, Bang YJ, Mainwaring P, Ng C, Chang JW, Kwong P, et al. Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy. Asia Pac J Clin Oncol. 2014;10(3):237–45. https://doi.org/10.1111/ajco.12163.CrossRefPubMed

18.

Poprach A, Pavlik T, Melichar B, Puzanov I, Dusek L, Bortlicek Z, et al. Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2012;23(12):3137–43. https://doi.org/10.1093/annonc/mds145.CrossRef

19.

Rautiola J, Donskov F, Peltola K, Joensuu H, Bono P. Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors of good prognosis in patients with metastatic renal cell carcinoma. BJU Int. 2014. https://doi.org/10.1111/bju.12940.

20.

Willemsen AE, Grutters JC, Gerritsen WR, van Erp NP, van Herpen CM, Tol J. mTOR inhibitor-induced interstitial lung disease in cancer patients: comprehensive review and a practical management algorithm. Int J Cancer J Int Cancer. 2016;138(10):2312–21. https://doi.org/10.1002/ijc.29887.CrossRef

21.

Tsukamoto T, Shinohara N, Tsuchiya N, Hamamoto Y, Maruoka M, Fujimoto H, et al. Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1. Jpn J Clin Oncol. 2011;41(1):17–24. https://doi.org/10.1093/jjco/hyq166.CrossRefPubMed

22.

Noguchi S, Masuda N, Iwata H, Mukai H, Horiguchi J, Puttawibul P, et al. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2. Breast Cancer. 2014;21(6):703–14. https://doi.org/10.1007/s12282-013-0444-8.CrossRefPubMed

23.

Atkinson BJ, Cauley DH, Ng C, Millikan RE, Xiao L, Corn P, et al. Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes. BJU Int. 2014;113(3):376–82. https://doi.org/10.1111/bju.12420.CrossRefPubMed

24.

Penttila P, Donskov F, Rautiola J, Peltola K, Laukka M, Bono P. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma. Eur J Cancer. 2017;81:9–16. https://doi.org/10.1016/j.ejca.2017.05.004.CrossRefPubMed

25.

Conteduca V, Santoni M, Medri M, Scarpi E, Burattini L, Lolli C, et al. Correlation of stomatitis and cutaneous toxicity with clinical outcome in patients with metastatic renal-cell carcinoma treated with everolimus. Clin Genitourin Cancer. 2016;14(5):426–31. https://doi.org/10.1016/j.clgc.2016.02.012.CrossRefPubMed

26.

Chu YH, Li H, Tan HS, Koh V, Lai J, Phyo WM, et al. Association of ABCB1 and FLT3 polymorphisms with toxicities and survival in Asian patients receiving sunitinib for renal cell carcinoma. PLoS ONE. 2015;10(8):e0134102. https://doi.org/10.1371/journal.pone.0134102.CrossRefPubMedPubMedCentral

27.

Diekstra MH, Klumpen HJ, Lolkema MP, Yu H, Kloth JS, Gelderblom H, et al. Association analysis of genetic polymorphisms in genes related to sunitinib pharmacokinetics, specifically clearance of sunitinib and SU12662. Clin Pharmacol Ther. 2014;96(1):81–9. https://doi.org/10.1038/clpt.2014.47.CrossRefPubMed

28.

Boudou-Rouquette P, Narjoz C, Golmard JL, Thomas-Schoemann A, Mir O, Taieb F, et al. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study. PLoS ONE. 2012;7(8):e42875. https://doi.org/10.1371/journal.pone.0042875.CrossRefPubMedPubMedCentral

29.

Bins S, Lenting A, El Bouazzaoui S, van Doorn L, Oomen-de Hoop E, Eskens FA, et al. Polymorphisms in SLCO1B1 and UGT1A1 are associated with sorafenib-induced toxicity. Pharmacogenomics. 2016;17(14):1483–90. https://doi.org/10.2217/pgs-2016-0063.CrossRefPubMed

30.

Suttle AB, Ball HA, Molimard M, Hutson TE, Carpenter C, Rajagopalan D, et al. Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma. Br J Cancer. 2014;111(10):1909–16. https://doi.org/10.1038/bjc.2014.503.CrossRefPubMedPubMedCentral

31.

van Erp NP, Eechoute K, van der Veldt AA, Haanen JB, Reyners AK, Mathijssen RH, et al. Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity. J Clin Oncol. 2009;27(26):4406–12. https://doi.org/10.1200/JCO.2008.21.7679.CrossRefPubMed

32.

Numakura K, Tsuchiya N, Kagaya H, Takahashi M, Tsuruta H, Inoue T, et al. Clinical effects of single nucleotide polymorphisms on drug-related genes in Japanese metastatic renal cell carcinoma patients treated with sunitinib. Anticancer Drugs. 2017;28(1):97–103. https://doi.org/10.1097/cad.0000000000000425.CrossRefPubMed

33.

Kim HR, Park HS, Kwon WS, Lee JH, Tanigawara Y, Lim SM, et al. Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients. Cancer Chemother Pharmacol. 2013;72(4):825–35. https://doi.org/10.1007/s00280-013-2258-y.CrossRefPubMed

34.

Mizuno T, Fukudo M, Terada T, Kamba T, Nakamura E, Ogawa O, et al. Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics. Drug Metab Pharmacokinet. 2012;27(6):631–9.CrossRefPubMed

35.

Noda S, Otsuji T, Baba M, Yoshida T, Kageyama S, Okamoto K, et al. Assessment of sunitinib-induced toxicities and clinical outcomes based on therapeutic drug monitoring of sunitinib for patients with renal cell carcinoma. Clin Genitourin Cancer. 2015;13(4):350–8. https://doi.org/10.1016/j.clgc.2015.01.007.CrossRefPubMed

36.

Fukudo M, Ito T, Mizuno T, Shinsako K, Hatano E, Uemoto S, et al. Exposure-toxicity relationship of sorafenib in Japanese patients with renal cell carcinoma and hepatocellular carcinoma. Clin Pharmacokinet. 2014;53(2):185–96. https://doi.org/10.1007/s40262-013-0108-z.CrossRefPubMed

37.

Mai H, Huang J, Zhang Y, Qu N, Qu H, Mei GH, et al. In-vivo relation between plasma concentration of sorafenib and its safety in Chinese patients with metastatic renal cell carcinoma: a single-center clinical study. Oncotarget. 2017;8(26):43458–69. https://doi.org/10.18632/oncotarget.16465.CrossRefPubMedPubMedCentral

38.

Lee JH, Chung YH, Kim JA, Shim JH, Lee D, Lee HC, et al. Genetic predisposition of hand-foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma. Cancer. 2013;119(1):136–42. https://doi.org/10.1002/cncr.27705.CrossRefPubMed

39.

Peer CJ, Sissung TM, Kim A, Jain L, Woo S, Gardner ER, et al. Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia. Clin Cancer Res. 2012;18(7):2099–107. https://doi.org/10.1158/1078-0432.CCR-11-2484.CrossRefPubMed

40.

Jain L, Sissung TM, Danesi R, Kohn EC, Dahut WL, Kummar S, et al. Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib. J Exp Clin Cancer Res CR. 2010;29:95. https://doi.org/10.1186/1756-9966-29-95.CrossRefPubMed

41.

Diekstra MH, Swen JJ, Boven E, Castellano D, Gelderblom H, Mathijssen RH, et al. CYP3A5 and ABCB1 polymorphisms as predictors for sunitinib outcome in metastatic renal cell carcinoma. Eur Urol. 2015;68(4):621–9. https://doi.org/10.1016/j.eururo.2015.04.018.CrossRefPubMed

42.

Qin C, Cao Q, Li P, Wang S, Wang J, Wang M, et al. The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma. Sci Rep. 2016;6:20089. https://doi.org/10.1038/srep20089.CrossRefPubMedPubMedCentral

43.

Zhang J, Yang J, Chen Y, Mao Q, Li S, Xiong W, et al. Genetic variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) are associated with Glioma Risk in a Han Chinese population: a case-control study. Mol Neurobiol. 2016;53(4):2610–8. https://doi.org/10.1007/s12035-015-9240-0.CrossRefPubMed

44.

Huez I, Creancier L, Audigier S, Gensac MC, Prats AC, Prats H. Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA. Mol Cell Biol. 1998;18(11):6178–90.CrossRefPubMedPubMedCentral

45.

Wang Y, Zheng Y, Zhang W, Yu H, Lou K, Zhang Y, et al. Polymorphisms of KDR gene are associated with coronary heart disease. J Am Coll Cardiol. 2007;50(8):760–7. https://doi.org/10.1016/j.jacc.2007.04.074.CrossRefPubMed

46.

Yamamoto K, Shinomiya K, Ioroi T, Hirata S, Harada K, Suno M, et al. Association of single nucleotide polymorphisms in STAT3 with hand-foot skin reactions in patients with metastatic renal cell carcinoma treated with multiple tyrosine kinase inhibitors: a retrospective analysis in Japanese patients. Targ Oncol. 2016;11(1):93–9. https://doi.org/10.1007/s11523-015-0382-9.CrossRef

47.

Tsuchiya N, Narita S, Inoue T, Hasunuma N, Numakura K, Horikawa Y, et al. Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma. Anticancer Drugs. 2013;24(3):310–4. https://doi.org/10.1097/CAD.0b013e32835c401c.CrossRefPubMed

48.

Franke RM, Lancaster CS, Peer CJ, Gibson AA, Kosloske AM, Orwick SJ, et al. Effect of ABCC2 (MRP2) transport function on erythromycin metabolism. Clin Pharmacol Ther. 2011;89(5):693–701. https://doi.org/10.1038/clpt.2011.25.CrossRefPubMedPubMedCentral

49.

Liu Y, Yin Y, Sheng Q, Lu X, Wang F, Lin Z, et al. Association of ABCC2 -24C > T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. PLoS ONE. 2014;9(1):e82681. https://doi.org/10.1371/journal.pone.0082681.CrossRefPubMedPubMedCentral

50.

Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, et al. Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(19):6062–9. https://doi.org/10.1158/1078-0432.CCR-09-0048.CrossRef

51.

Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, et al. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med. 2003;9(2):220–4. https://doi.org/10.1038/nm815.CrossRefPubMed

52.

Bartnicka L, Kurzawski M, Drozdzik A, Plonska-Gosciniak E, Gornik W, Drozdzik M. Effect of ABCB1 (MDR1) 3435C > T and 2677G > A, T polymorphisms and P-glycoprotein inhibitors on salivary digoxin secretion in congestive heart failure patients. Pharmacol Rep PR. 2007;59(3):323–9.PubMed

53.

Huber JC, Schneeberger C, Tempfer CB. Genetic modeling of estrogen metabolism as a risk factor of hormone-dependent disorders. Maturitas. 2002;41(Suppl 1):S55–64.CrossRefPubMed

54.

Lakkireddy S, Aula S, Avn S, Kapley A, Rao Digumarti R, Jamil K. Association of the common CYP1A1*2C Variant (Ile462Val polymorphism) with chronic myeloid leukemia (CML) in patients undergoing imatinib therapy. Cell J. 2015;17(3):510–9.PubMedPubMedCentral

55.

Watanabe A, Yamamoto K, Ioroi T, Hirata S, Harada K, Miyake H, et al. Association of single nucleotide polymorphisms in STAT3, ABCB1, and ABCG2 with stomatitis in patients with metastatic renal cell carcinoma treated with sunitinib: a retrospective analysis in Japanese patients. Biol Pharm Bull. 2017;40(4):458–64. https://doi.org/10.1248/bpb.b16-00875.CrossRefPubMed

56.

Garcia-Donas J, Esteban E, Leandro-Garcia LJ, Castellano DE, del Alba AG, Climent MA, et al. Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. Lancet Oncol. 2011;12(12):1143–50. https://doi.org/10.1016/s1470-2045(11)70266-2.CrossRefPubMed

57.

Choi HY, Bae KS, Cho SH, Ghim JL, Choe S, Jung JA, et al. Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid. Pharmacogenet Genomics. 2015;25(12):595–608. https://doi.org/10.1097/fpc.0000000000000176.CrossRefPubMed

58.

Keskitalo JE, Pasanen MK, Neuvonen PJ, Niemi M. Different effects of the ABCG2 c.421C > A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin. Pharmacogenomics. 2009;10(10):1617–24. https://doi.org/10.2217/pgs.09.85.CrossRefPubMed

59.

Diekstra MH, Belaustegui A, Swen JJ, Boven E, Castellano D, Gelderblom H, et al. Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma. Pharmacogenomics J. 2017;17(1):42–6. https://doi.org/10.1038/tpj.2015.100.CrossRefPubMed

60.

He HR, Sun JY, Ren XD, Wang TT, Zhai YJ, Chen SY, et al. Effects of CYP3A4 polymorphisms on the plasma concentration of voriconazole. Eur J Clin Microbiol Infect Dis. 2015;34(4):811–9. https://doi.org/10.1007/s10096-014-2294-5.CrossRefPubMed

61.

Choi JW, Park CS, Hwang M, Nam HY, Chang HS, Park SG, et al. A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli. J Allergy Clin Immunol. 2008;122(6):1119–26 e7. https://doi.org/10.1016/j.jaci.2008.09.026.CrossRef

62.

Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ. Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol. 2010;66(2):357–71. https://doi.org/10.1007/s00280-009-1170-y.CrossRefPubMed

63.

Kim JJ, Vaziri SAJ, Rini BI, Elson P, Garcia JA, Wirka R, 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(7):1946–54. https://doi.org/10.1002/cncr.26491.CrossRefPubMed

64.

Diekstra MH, Liu X, Swen JJ, Boven E, Castellano D, Gelderblom H, et al. Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma. Eur J Clin Pharmacol. 2015;71(12):1477–84. https://doi.org/10.1007/s00228-015-1935-7.CrossRefPubMedPubMedCentral

65.

Hacking D, Knight JC, Rockett K, Brown H, Frampton J, Kwiatkowski DP, et al. Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. Genes Immun. 2004;5(4):274–82. https://doi.org/10.1038/sj.gene.6364067.CrossRefPubMed

66.

Amaya MP, Criado L, Blanco B, Gomez M, Torres O, Florez L, et al. Polymorphisms of pro-inflammatory cytokine genes and the risk for acute suppurative or chronic nonsuppurative apical periodontitis in a Colombian population. Int Endod J. 2013;46(1):71–8. https://doi.org/10.1111/j.1365-2591.2012.02097.x.CrossRefPubMed

67.

Xu CF, Johnson T, Garcia-Donas J, Choueiri TK, Sternberg CN, Davis ID, et al. IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma. Br J Cancer. 2015;112(7):1190–8. https://doi.org/10.1038/bjc.2015.64.CrossRefPubMedPubMedCentral

68.

Petreaca ML, Yao M, Liu Y, Defea K, Martins-Green M. Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8/CXCL8) is required for IL-8/CXCL8-induced endothelial permeability. Mol Biol Cell. 2007;18(12):5014–23. https://doi.org/10.1091/mbc.E07-01-0004.CrossRefPubMedPubMedCentral

69.

Martin D, Galisteo R, Gutkind JS. CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. J Biol Chem. 2009;284(10):6038–42. https://doi.org/10.1074/jbc.C800207200.CrossRefPubMedPubMedCentral

70.

Xu CF, Reck BH, Xue Z, Huang L, Baker KL, Chen M, et al. Pazopanib-induced hyperbilirubinemia is associated with Gilbert’s syndrome UGT1A1 polymorphism. Br J Cancer. 2010;102(9):1371–7. https://doi.org/10.1038/sj.bjc.6605653.CrossRefPubMedPubMedCentral

71.

Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. New Engl J Med. 1995;333(18):1171–5. https://doi.org/10.1056/nejm199511023331802.CrossRefPubMed

72.

Zucker SD, Qin X, Rouster SD, Yu F, Green RM, Keshavan P, et al. Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci USA. 2001;98(22):12671–6. https://doi.org/10.1073/pnas.231140698.CrossRefPubMedPubMedCentral

73.

Danoff TM, Campbell DA, McCarthy LC, Lewis KF, Repasch MH, Saunders AM, et al. A Gilbert’s syndrome UGT1A1 variant confers susceptibility to tranilast-induced hyperbilirubinemia. Pharmacogenomics J. 2004;4(1):49–53. https://doi.org/10.1038/sj.tpj.6500221.CrossRefPubMed

74.

Singer JB, Shou Y, Giles F, Kantarjian HM, Hsu Y, Robeva AS, et al. UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia. 2007;21(11):2311–5. https://doi.org/10.1038/sj.leu.2404827.CrossRefPubMed

75.

Low SK, Fukunaga K, Takahashi A, Matsuda K, Hongo F, Nakanishi H, et al. Association study of a functional variant on ABCG2 gene with sunitinib-induced severe adverse drug reaction. PLoS ONE. 2016;11(2):e0148177. https://doi.org/10.1371/journal.pone.0148177.CrossRefPubMedPubMedCentral

76.

Xu CF, Reck BH, Goodman VL, Xue Z, Huang L, Barnes MR, et al. Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma. J Hepatol. 2011;54(6):1237–43. https://doi.org/10.1016/j.jhep.2010.09.028.CrossRefPubMed

77.

Olynyk JK, Knuiman MW, Divitini ML, Bartholomew HC, Cullen DJ, Powell LW. Effects of HFE gene mutations and alcohol on iron status, liver biochemistry and morbidity. J Gastroenterol Hepatol. 2005;20(9):1435–41. https://doi.org/10.1111/j.1440-1746.2005.03967.x.CrossRefPubMed

78.

Nelson JE, Bhattacharya R, Lindor KD, Chalasani N, Raaka S, Heathcote EJ, et al. HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis. Hepatology. 2007;46(3):723–9. https://doi.org/10.1002/hep.21742.CrossRefPubMed

79.

Forooghian F, Das B. Anti-angiogenic effects of ribonucleic acid interference targeting vascular endothelial growth factor and hypoxia-inducible factor-1alpha. Am J Ophthalmol. 2007;144(5):761–8. https://doi.org/10.1016/j.ajo.2007.07.022.CrossRefPubMed

80.

Xu CF, Johnson T, Wang X, Carpenter C, Graves AP, Warren L, et al. HLA-B*57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer. Clin Cancer Res. 2016;22(6):1371–7. https://doi.org/10.1158/1078-0432.CCR-15-2044.CrossRefPubMed

81.

Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002;166(7):916–9. https://doi.org/10.1164/rccm.2108091.CrossRefPubMed

82.

Hirata K, Takagi H, Yamamoto M, Matsumoto T, Nishiya T, Mori K, et al. Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J. 2008;8(1):29–33. https://doi.org/10.1038/sj.tpj.6500442.CrossRefPubMed

83.

O’Donohue J, Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut. 2000;47(5):717–20.CrossRefPubMedPubMedCentral

84.

Kindmark A, Jawaid A, Harbron CG, Barratt BJ, Bengtsson OF, Andersson TB, et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J. 2008;8(3):186–95. https://doi.org/10.1038/sj.tpj.6500458.CrossRefPubMed

85.

Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41(7):816–9. https://doi.org/10.1038/ng.379.CrossRefPubMed

86.

Zimmerman EI, Hu S, Roberts JL, Gibson AA, Orwick SJ, Li L, et al. Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013;19(6):1458–66. https://doi.org/10.1158/1078-0432.CCR-12-3306.CrossRefPubMedPubMedCentral

87.

Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A. Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014;110(4):894–8. https://doi.org/10.1038/bjc.2013.811.CrossRefPubMedPubMedCentral

88.

Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011;63(1):157–81. https://doi.org/10.1124/pr.110.002857.CrossRefPubMed

89.

Maayah ZH, Ansari MA, El Gendy MA, Al-Arifi MN, Korashy HM. Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway. Arch Toxicol. 2014;88(3):725–38. https://doi.org/10.1007/s00204-013-1159-5.PubMed

90.

Maayah ZH, El Gendy MA, El-Kadi AO, Korashy HM. Sunitinib, a tyrosine kinase inhibitor, induces cytochrome P450 1A1 gene in human breast cancer MCF7 cells through ligand-independent aryl hydrocarbon receptor activation. Arch Toxicol. 2013;87(5):847–56. https://doi.org/10.1007/s00204-012-0996-y.CrossRefPubMed

91.

Lu J, Zhao Q, Zhai YJ, He HR, Yang LH, Gao F, et al. Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis. OncoTargets Ther. 2015;8:2883–902. https://doi.org/10.2147/OTT.S92259.CrossRef

92.

Han F, Tan Y, Cui W, Dong L, Li W. Novel insights into etiologies of leukemia: a HuGE review and meta-analysis of CYP1A1 polymorphisms and leukemia risk. Am J Epidemiol. 2013;178(4):493–507. https://doi.org/10.1093/aje/kwt016.CrossRefPubMed

93.

Crofts F, Taioli E, Trachman J, Cosma GN, Currie D, Toniolo P, et al. Functional significance of different human CYP1A1 genotypes. Carcinogenesis. 1994;15(12):2961–3.CrossRefPubMed

94.

van der Veldt AA, Eechoute K, Gelderblom H, Gietema J, Guchelaar HJ, van Erp NP, et al. Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib. Clin Cancer Res. 2011;17(3):620–9. https://doi.org/10.1158/1078-0432.ccr-10-1828.CrossRefPubMed

95.

Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P, et al. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. 1996;87(3):1089–96.PubMed

96.

Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10(12):1911–8.PubMed

97.

Pascual T, Apellaniz-Ruiz M, Pernaut C, Cueto-Felgueroso C, Villalba P, Alvarez C, et al. Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer. PLoS ONE. 2017;12(7):e0180192. https://doi.org/10.1371/journal.pone.0180192.CrossRefPubMedPubMedCentral

98.

de Velasco G, Gray KP, Hamieh L, Urun Y, Carol HA, Fay AP, et al. Pharmacogenomic markers of targeted therapy toxicity in patients with metastatic renal cell carcinoma. Eur Urol Focus. 2016;2(6):633–9. https://doi.org/10.1016/j.euf.2016.03.017.CrossRefPubMedPubMedCentral

Title: Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma
Authors: Kazuhiro Yamamoto
Ikuko Yano
Publication date: 01-02-2018
Publisher: Springer US
Published in: Medical Oncology / Issue 2/2018
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-017-1077-0

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com