1,111
Views
5
CrossRef citations to date
0
Altmetric
Review Article

Genetic and ethnic modulation of cardiovascular toxicity of vascular endothelial growth factor inhibitors

, , &
Pages 46-56 | Received 07 Jul 2017, Accepted 13 Sep 2017, Published online: 27 Sep 2017

References

  • Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15:385–403.
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342.
  • Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–124.
  • Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.
  • Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. JCO. 2010;28:1061–1068.
  • Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet (London, England). 2011;378:1931–1939.
  • Li W, Croce K, Steensma DP, et al. Vascular and metabolic implications of novel targeted cancer therapies: focus on kinase inhibitors. J Am Coll Cardiol. 2015;66:1160–1178.
  • Lankhorst S, Saleh L, Danser AJ, et al. Etiology of angiogenesis inhibition-related hypertension. Curr Opin Pharmacol. 2015;21:7–13.
  • Common Terminology Criteria for Adverse Events v4.0. National Cancer Institute; 2009.
  • Bellinger AM, Arteaga CL, Force T, et al. Cardio-oncology: how new targeted cancer therapies and precision medicine can inform cardiovascular discovery. Circulation. 2015;132:2248–2258.
  • Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375:1457–1467.
  • Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358:1129–1136.
  • Patel TV, Morgan JA, Demetri GD, et al. A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J Natl Cancer Inst. 2008;100:282–284.
  • Vigneau C, Lorcy N, Dolley-Hitze T, et al. All anti-vascular endothelial growth factor drugs can induce ‘pre-eclampsia-like syndrome’: a RARe study. Nephrol Dial Transplant. 2014;29:325–332.
  • Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123:2856–2869.
  • Patten IS, Rana S, Shahul S, et al. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature. 2012;485:333–338.
  • Overexpression of vascular endothelial growth factor 165 (VEGF165) protects cardiomyocytes against doxorubicin-induced apoptosis. J Chemother. 2010;22:402–406.
  • Räsänen M, Degerman J, Nissinen TA, et al. VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection. Proc Natl Acad Sci USA. 2016;113:13144–13149.
  • Pepe M, Mamdani M, Zentilin L, et al. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy. Circ Res. 2010;106:1893–1903.
  • Zhao T, Zhao W, Meng W, et al. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium. Am J Transl Res. 2015;7:697–709.
  • Di Lisi D, Madonna R, Zito C, et al. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond. Int J Cardiol. 2017;227:11–17.
  • Ghatalia P, Morgan CJ, Je Y, et al. Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Critic Rev Oncol/Hematol. 2015;94:228–237.
  • Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7:332–344.
  • Cheng H, Force T. Why do kinase inhibitors cause cardiotoxicity and what can be done about it? Prog Cardiovasc Dis. 2010;53:114–120.
  • Sanguinetti MC, Mitcheson JS. Predicting drug-hERG channel interactions that cause acquired long QT syndrome. Trends Pharmacol Sci. 2005;26:119–124.
  • Katchman AN, Koerner J, Tosaka T, et al. Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. 2006;316:1098–1106.
  • Yang T, Roden DM. Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence. Circulation. 1996;93:407–411.
  • Kupershmidt S, Yang IC, Hayashi K, et al. The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines. FASEB J. 2003;17:2263–2265.
  • Shah RR, Morganroth J, Shah DR. Cardiovascular safety of tyrosine kinase inhibitors: with a special focus on cardiac repolarisation (QT interval). Drug Saf. 2013;36:295–316.
  • Kramer B, Brill M, Bruhn A, et al. Relationship between the degree of coronary artery disease and of left ventricular function and the duration of the QT-interval in ECG. Eur Heart J. 1986;7:14–24.
  • Hart G. Cellular electrophysiology in cardiac hypertrophy and failure. Cardiovasc Res. 1994;28:933–946.
  • Davey PP, Barlow C, Hart G. Prolongation of the QT interval in heart failure occurs at low but not at high heart rates. Clin Sci. 2000;98:603–610.
  • Harada M, Tadevosyan A, Qi X, et al. Atrial fibrillation activates AMP-dependent protein kinase and its regulation of cellular calcium handling: potential role in metabolic adaptation and prevention of progression. J Am Coll Cardiol. 2015;66:47–58.
  • An MM, Zou Z, Shen H, et al. Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis. Eur J Clin Pharmacol. 2010;66:813–821.
  • Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncologica (Stockholm, Sweden). 2009;48:9–17.
  • Wu S, Chen JJ, Kudelka A, et al. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol. 2008;9:117–123.
  • Qi WX, Lin F, Sun YJ, et al. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71:431–439.
  • Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372:621–630.
  • Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (London, England). 2014;383:31–39.
  • Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. JCO. 2012;30:3499–3506.
  • Donskov F, Michaelson MD, Puzanov I, et al. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients. Br J Cancer. 2015;113:1571–1580.
  • Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2011;103:763–773.
  • Estfan B, Byrne M, Kim R. Sorafenib in advanced hepatocellular carcinoma: hypertension as a potential surrogate marker for efficacy. Am J Clin Oncol. 2013;36:319–324.
  • Mir O, Coriat R, Cabanes L, et al. An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity. The Oncologist. 2011;16:1325–1332.
  • Dahlberg SE, Sandler AB, Brahmer JR, et al. Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. JCO. 2010;28:949–954.
  • Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. JCO. 2008;26:4672–4678.
  • Ryanne Wu R, Lindenberg PA, Slack R, et al. Evaluation of hypertension as a marker of bevacizumab efficacy. J Gastrointest Cancer. 2009;40:101–108.
  • Scartozzi M, Galizia E, Chiorrini S, et al. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol. 2009;20:227–230.
  • Hurwitz HI, Douglas PS, Middleton JP, et al. Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies. The Oncologist. 2013;18:273–280.
  • Duffaud F, Sleijfer S, Litiere S, et al. Hypertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on european organisation for research and treatment of cancer (EORTC) 62043 and 62072 trials. Eur J Cancer (Oxford, England: 1990). 2015;51:2615–2623.
  • Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99:1232–1239.
  • Schutz FA, Je Y, Azzi GR, et al. Bevacizumab increases the risk of arterial ischemia: a large study in cancer patients with a focus on different subgroup outcomes. Ann Oncol. 2011;22:1404–1412.
  • Ranpura V, Hapani S, Chuang J, et al. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncologica (Stockholm, Sweden). 2010;49:287–297.
  • Choueiri TK, Schutz FA, Je Y, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. JCO. 2010;28:2280–2285.
  • Nalluri SR, Chu D, Keresztes R, et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008;300:2277–2285.
  • Hurwitz HI, Saltz LB, Van Cutsem E, et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. JCO. 2011;29:1757–1764.
  • Sonpavde G, Je Y, Schutz F, et al. Venous thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2013;87:80–89.
  • Choueiri TK, Mayer EL, Je Y, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. JCO. 2011;29:632–638.
  • Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet (London, England). 2007;370:2011–2019.
  • Shamloo BK, Chhabra P, Freedman AN, et al. Novel adverse events of bevacizumab in the US FDA adverse event reporting system database: a disproportionality analysis. Drug Safety. 2012;35:507–518.
  • Ghatalia P, Je Y, Kaymakcalan MD, et al. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Br J Cancer. 2015;112:296–305.
  • Bello CL, Mulay M, Huang X, et al. Electrocardiographic characterization of the QTc interval in patients with advanced solid tumors: pharmacokinetic- pharmacodynamic evaluation of sunitinib. Clin Cancer Res. 2009;15:7045–7052.
  • Polite BN, Sing A, Sargent DJ, et al. Exploring racial differences in outcome and treatment for metastatic colorectal cancer: results from a large prospective observational cohort study (BRiTE). Cancer. 2012;118:1083–1090.
  • Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003;290:199–206.
  • Selassie A, Wagner CS, Laken ML, et al. Progression is accelerated from prehypertension to hypertension in blacks. Hypertension (Dallas, TX: 1979). 2011;58:579–587.
  • Carson AP, Howard G, Burke GL, et al. Ethnic differences in hypertension incidence among middle-aged and older adults: the multi-ethnic study of atherosclerosis. Hypertension (Dallas, TX: 1979). 2011;57:1101–1107.
  • Chen Z, Zhong B, Lun X, et al. Specific safety profile of bevacizumab in asian patients with advanced NSCLC: a meta-analysis. Medicine. 2015;94:e975.
  • Ueda T, Uemura H, Tomita Y, et al. Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial. Japanese J Clin Oncol. 2013;43:616–628.
  • Lee SH, Bang YJ, Mainwaring P, et al. Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy. Asia-Pac J Clin Oncol. 2014;10:237–245.
  • Chen Y, Suzuki A, Tortorici MA, et al. Axitinib plasma pharmacokinetics and ethnic differences. Invest New Drugs. 2015;33:521–532.
  • Schneider BP, Li L, Shen F, et al. Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014;111:1241–1248.
  • Sibertin-Blanc C, Mancini J, Fabre A, et al. Vascular endothelial growth factor a c.*237C > T polymorphism is associated with bevacizumab efficacy and related hypertension in metastatic colorectal cancer. Digest Liver Dis. 2015;47:331–337.
  • Etienne-Grimaldi MC, Formento P, Degeorges A, et al. Prospective analysis of the impact of VEGF-A gene polymorphisms on the pharmacodynamics of bevacizumab-based therapy in metastatic breast cancer patients. Br J Clin Pharmacol. 2011;71:921–928.
  • Morita S, Uehara K, Nakayama G, et al. Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer. Cancer Chemother Pharmacol. 2013;71:405–411.
  • Lambrechts D, Moisse M, Delmar P, et al. Genetic markers of bevacizumab-induced hypertension. Angiogenesis. 2014;17:685–694.
  • Kim HR, Park HS, Kwon WS, et al. Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients. Cancer Chemother Pharmacol. 2013;72:825–835.
  • Kim JJVS, Elson P, Rini BI, Ganapathi MK, Ganapathi R. VEGF single nucleotide polymorphisms (SNPs) and correlation to sunitinib-induced hypertension (HTN) in metastatic renal cell carcinoma (mRCC) patients (pts). J Clin Oncol. 2009;27(15S Suppl):5005.
  • Eechoute K, van der Veldt AA, Oosting S, et al. Polymorphisms in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) predict sunitinib-induced hypertension. Clin Pharmacol Ther. 2012;92:503–510.
  • Huang CL, Kuo E. Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension. Nat Clin Pract Nephrol. 2007;3:623–630.
  • Wilson FH, Disse-Nicodeme S, Choate KA, et al. Human hypertension caused by mutations in WNK kinases. Science (New York, NY). 2001;293:1107–1112.
  • Newhouse S, Farrall M, Wallace C, Hoti M, Burke B, Howard P, etet al. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion. PloS One. 2009;4:e5003.
  • Turner ST, Schwartz GL, Chapman AB, et al. WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension (Dallas, TX: 1979). 2005;46:758–765.
  • Staruschenko A, Palygin O, Ilatovskaya DV, et al. Epidermal growth factors in the kidney and relationship to hypertension. Am J Physiol Renal Physiol. 2013;305:F12–F20.
  • Wang Y, Zheng Y, Zhang W, et al. Polymorphisms of KDRGene are associated with coronary heart disease. J Am College Cardiol. 2007;50:760–767.
  • Kant R, Bali A, Singh N, et al. Prolyl 4 hydroxylase: a critical target in the pathophysiology of diseases. Korean J Physiol Pharmacol. 2013;17:111–120.
  • Chen Y, Dawes PT, Packham JC, et al. Interaction between smoking and polymorphism in the promoter region of the vegfa gene is associated with ischemic heart disease and myocardial infarction in rheumatoid arthritis. J Rheumatol. 2011;38:802–809.
  • Biselli PM, Guerzoni AR, de Godoy MF, et al. Vascular endothelial growth factor genetic variability and coronary artery disease in Brazilian population. Heart Vessels. 2008;23:371–375.
  • Howell WM, Ali S, Rose-Zerilli MJ, et al. VEGF polymorphisms and severity of atherosclerosis. J Med Genet. 2005;42:485–490.
  • Shahbazi M, Fryer AA, Pravica V, et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol. 2002;13:260–264.
  • Steffensen KD, Waldstrøm M, Brandslund I, et al. The relationship of VEGF polymorphisms with serum VEGF levels and progression-free survival in patients with epithelial ovarian cancer. Gynecol Oncol. 2010;117:109–116.
  • Prior SJ, Hagberg JM, Paton CM, Douglass LW, Brown MD, McLenithan JC, etet al. DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption. Am J Physiol. 2006;290:H1848–H1H55.
  • Oh SY, Kwon HC, Kim SH, et al. The relationship of vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer patients treated with FOLFOX: VEGF polymorphism in gastric cancer. BMC Cancer. 2013;13:43.
  • Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5’-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002;51:1635–1639.
  • Ozvegy-Laczka C, Cserepes J, Elkind NB, et al. Tyrosine kinase inhibitor resistance in cancer: role of ABC multidrug transporters. Drug Resist Updates. 2005;8:15–26.
  • Ozvegy-Laczka C, Hegedus T, Varady G, et al. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol. 2004;65:1485–1495.
  • Shukla S, Robey RW, Bates SE, et al. Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metabol Dispos. 2009;37:359–365.
  • Cascorbi I. Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacol Ther. 2006;112:457–473.
  • Kim KA, Joo HJ, Park JY. ABCG2 polymorphisms, 34G > A and 421C > A in a Korean population: analysis and a comprehensive comparison with other populations. J Clin Pharm Ther. 2010;35:705–712.
  • Keskitalo JE, Pasanen MK, Neuvonen PJ, et al. Different effects of the ABCG2 c.421C > A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin. Pharmacogenomics. 2009;10:1617–1624.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.