Paclitaxel-induced neuropathy: potential association of MAPT and GSK3B genotypes

BMC Cancer

Susanna B Park¹  John B Kwok⁴  Clement T Loy²  Michael L Friedlander³  Cindy S-Y Lin⁴  Arun V Krishnan⁴  Craig R Lewis³  Matthew C Kiernan¹ 

[1] Brain and Mind Research Institute, University of Sydney, Sydney, Australia

[2] School of Public Health, University of Sydney, Sydney, Australia

[3] Department of Medical Oncology, Prince of Wales Hospital, New South Wales, Australia

[4] School of Medical Sciences, University of New South Wales, New South Wales, Australia

关键词: GSK3β;    MAPT;    Neurotoxicity;    Neuropathy;    Paclitaxel;   

Others  :  1106784
DOI  :  10.1186/1471-2407-14-993

 received in 2014-04-24, accepted in 2014-12-16,  发布年份 2014

【 摘 要 】

Background

Paclitaxel treatment produces dose-limiting peripheral neurotoxicity, which adversely affects treatment and long-term outcomes. In the present study, the contribution of genetic polymorphisms to paclitaxel-induced neurotoxicity were assessed in 21 patients, focusing on polymorphisms involved in the tau-microtubule pathway, an important target of paclitaxel involved in neurotoxicity development.

Methods

Polymorphisms in the microtubule-associated protein tau (MAPT) gene (haplotype 1 and rs242557 polymorphism) and the glycogen synthase kinase-3β (GSK3β) gene (rs6438552 polymorphism) were investigated. Neurotoxicity was assessed using neuropathy grading scales, neurophysiological studies and patient questionnaires.

Results

A significant relationship between the GSK-3B rs6438552 polymorphism and paclitaxel-induced neurotoxicity was evident.

Conclusions

Polymorphisms in tau-associated genes may contribute to the development of paclitaxel-induced neurotoxicity, although larger series will be necessary to confirm these findings.

【 授权许可】

   
2014 Park et al.; licensee BioMed Central.

【 参考文献 】

• [1]Rao S, He L, Chakravarty S, Ojima I, Orr GA, Horwitz SB: Characterization of the Taxol binding site on the microtubule. Identification of Arg(282) in beta-tubulin as the site of photoincorporation of a 7-benzophenone analogue of Taxol. J Biol Chem 1999, 274:37990-37994.
• [2]Baas PW, Ahmad FJ: Beyond taxol: microtubule-based treatment of disease and injury of the nervous system. Brain 2013, 136:2937-2951.
• [3]Rowinsky EK, Donehower RC: Paclitaxel (taxol). N Engl J Med 1995, 332:1004-1014.
• [4]Jimenez-Andrade JM, Peters CM, Mejia NA, Ghilardi JR, Kuskowski MA, Mantyh PW: Sensory neurons and their supporting cells located in the trigeminal, thoracic and lumbar ganglia differentially express markers of injury following intravenous administration of paclitaxel in the rat. Neurosci Lett 2006, 405:62-67.
• [5]Theiss C, Meller K: Taxol impairs anterograde axonal transport of microinjected horseradish peroxidase in dorsal root ganglia neurons in vitro. Cell Tissue Res 2000, 299:213-224.
• [6]Myers AJ, Pittman AM, Zhao AS, Rohrer K, Kaleem M, Marlowe L, Lees A, Leung D, McKeith IG, Perry RH, Morris CM, Trojanowski JQ, Clark C, Karlawish J, Arnold S, Forman MS, Van Deerlin V, de Silva R, Hardy J: The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts. Neurobiol Dis 2007, 25:561-70.
• [7]Baker M, Litvan I, Houlden H, Adamson J, Dickson D, Perez-Tur J, Hardy J, Lynch T, Bigio E, Hutton M: Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Human Mol Genet 1999, 8:711-715.
• [8]Kwok JB, Teber ET, Loy C, Hallupp M, Nicholson G, Mellick GD, Buchanan DD, Silburn PA, Schofield PR: Tau haplotypes regulate transcription and are associated with Parkinson's disease. Ann Neurol 2004, 55:329-334.
• [9]Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L: Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 2005, 102:8315-20.
• [10]Lovestone S, Reynolds CH, Latimer D, Davis DR, Anderton BH, Gallo JM, Hanger D, Mulot S, Marquardt B, Stabel S: Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Current Biology 1994, 4:1077-1086.
• [11]Fu Y, Hu D, Qiu J, Xie X, Ye F, Lu WG: Overexpression of glycogen synthase kinase-3 in ovarian carcinoma cells with acquired paclitaxel resistance. Int J Gynecol Cancer 2011, 21:439-444.
• [12]Ross JL, Santangelo CD, Makrides V, Fygenson DK: Tau induces cooperative Taxol binding to microtubules. Proc Natl Acad Sci USA 2004, 101:12910-12915.
• [13]Kar S, Fan J, Smith MJ, Goedert M, Amos LA: Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. The EMBO journal 2003, 22:70-77.
• [14]Cavaletti G, Frigeni B, Lanzani F, Piatti M, Rota S, Briani C, Zara G, Plasmati R, Pastorelli F, Caraceni A, Pace A, Manicone M, Lissoni A, Colombo N, Bianchi G, Zanna C, Italian NETox Group: The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute- Common Toxicity Scale. J Peripher Nerv Syst 2007, 12:210-5.
• [15]Park SB, Lin CS, Krishnan AV, Friedlander ML, Lewis CR, Kiernan MC: Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy. Muscle Nerve 2011, 43:367-374.
• [16]de Graan AJ, Elens L, Sprowl JA, Sparreboom A, Friberg LE, van der Holt B, de Raaf PJ, de Bruijn P, Engels FK, Eskens FA, Wiemer EA, Verweij J, Mathijssen RH, van Schaik RH: CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity. Clin Cancer Res 2013, 19:3316-24.
• [17]Sucheston LE, Zhao H, Yao S, Zirpoli G, Liu S, Barlow WE, Moore HC, Thomas Budd G, Hershman DL, Davis W, Ciupak GL, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Livingston RB, Albain KS, Hayes DF, Ambrosone CB: Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trials (S0221). Breast Cancer Res Treat 2011, 130:993-1002.
• [18]Abraham JE, Guo Q, Dorling L, Tyrer J, Ingle S, Hardy R, Vallier AL, Hiller L, Burns R, Jones L, Bowden SJ, Dunn JA, Poole CJ, Caldas C, Pharoah PP, Earl HM: Replication of genetic polymorphisms reported to be associated with taxane-related sensory neuropathy in patients with early breast cancer treated with Paclitaxel. Clin Cancer Res 2014, 20:2466-75.
• [19]Leskelä S, Jara C, Leandro-García LJ, Martínez A, García-Donas J, Hernando S, Hurtado A, Vicario JC, Montero-Conde C, Landa I, López-Jiménez E, Cascón A, Milne RL, Robledo M, Rodríguez-Antona C: Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity. Pharmacogenomics J 2011, 11:121-9.
• [20]Hertz DL, Motsinger-Reif AA, Drobish A, Winham SJ, McLeod HL, Carey LA, Dees EC: CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Breast Cancer Res Treat 2012, 134:401-410.
• [21]Wheeler HE, Gamazon ER, Wing C, Njiaju UO, Njoku C, Baldwin RM, Owzar K, Jiang C, Watson D, Shterev I, Kubo M, Zembutsu H, Winer EP, Hudis CA, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL, Cox NJ, Dolan ME, Cancer and Leukemia Group B: Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy. Clin Cancer Res 2013, 19:491-9.
• [22]Baldwin RM, Owzar K, Zembutsu H, Chhibber A, Kubo M, Jiang C, Watson D, Eclov RJ, Mefford J, McLeod HL, Friedman PN, Hudis CA, Winer EP, Jorgenson EM, Witte JS, Shulman LN, Nakamura Y, Ratain MJ, Kroetz DL: A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res 2012, 18:5099-109.
• [23]Leandro-García LJ, Inglada-Pérez L, Pita G, Hjerpe E, Leskelä S, Jara C, Mielgo X, González-Neira A, Robledo M, Avall-Lundqvist E, Gréen H, Rodríguez-Antona C: Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. J Med Genet 2013, 50:599-605.
• [24]McWhinney-Glass S, Winham SJ, Hertz DL, Yen Revollo J, Paul J, He Y, Brown R, Motsinger-Reif AA, McLeod HL, Scottish Gynaecological Clinical Trials Group: Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity. Clin Cancer Res 2013, 19:5769-76.
• [25]Leandro-García LJ, Leskelä S, Jara C, Gréen H, Avall-Lundqvist E, Wheeler HE, Dolan ME, Inglada-Perez L, Maliszewska A, de Cubas AA, Comino-Méndez I, Mancikova V, Cascón A, Robledo M, Rodríguez-Antona C: Regulatory polymorphisms in β-tubulin IIa are associated with paclitaxel-induced peripheral neuropathy. Clin Cancer Res 2012, 18:4441-8.
• [26]Sève P, Reiman T, Isaac S, Trillet-Lenoir V, Lafanechere L, Sawyer M, Dumontet C: Protein abundance of class III beta-tubulin but not Delta2-alpha-tubulin or tau is related to paclitaxel response in carcinomas of unknown primary site. Anticancer Res 2008, 28:1161-1167.
• [27]Kwok JB, Loy CT, Hamilton G, Lau E, Hallupp M, Williams J, Owen MJ, Broe GA, Tang N, Lam L, Powell JF, Lovestone S, Schofield PR: Glycogen synthase kinase-3beta and tau genes interact in Alzheimer's disease. Ann Neurol 2008, 64:446-454.
• [28]Kwok JB, Hallupp M, Loy CT, Chan DK, Woo J, Mellick GD, Buchanan DD, Silburn PA, Halliday GM, Schofield PR: GSK3B polymorphisms alter transcription and splicing in Parkinson's disease. Ann Neurol 2005, 58:829-839.
• [29]Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, Lasrado R, Vandezande K, Laenen I, Boon T, Van Lint J, Vandenheede J, Moechars D, Loos R, Van Leuven F: Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. J Biol Chem 2000, 275:41340-9.
• [30]Hernandez F, Gomez de Barreda E, Fuster-Matanzo A, Lucas JJ, Avila J: GSK3: a possible link between beta amyloid peptide and tau protein. Exp Neurol 2010, 223:322-325.