Индуцированная таксанами периферическая нейропатия: механизм развития и фармакогенетические факторы

1. Тюляндин С.А., Гарин А.М., Горбунова В.А. Таксаны – новые противоопухолевые препараты растительного происхождения с уникальным механизмом действия. Вестн. РОНЦ им. Н.Н.Блохина РАМН. 1993; 4 (S): 96–101. / Tiuliandin S.A., Garin A.M., Gorbunova V.A. Taksany – novye protivoopukholevye preparaty rastitel'nogo proiskhozhdeniia s unikal'nym mekhanizmom deistviia. Vestn. RONTs im. N.N.Blokhina RAMN. 1993; 4 (S): 96–101. [in Russian]
2. Корман Д.Б. Основы противоопухолевой химиотерапии. М: Практическая медицина, 2006. / Korman D.B. Osnovy protivoopukholevoi khimioterapii. M: Prakticheskaia meditsina, 2006. [in Russian]
3. Roriguez-Antona C. Pharmacogenomics of paclitaxel. Pharmacogenomics 2010; 11 (5): 621–3.
4. Krens SD, McLeod HL, Hertz DL. Pharmacogenetics, enzyme probes and therapeutic drug monitoring as potential tools for individualizing taxane therapy. Pharmacogenomics 2013; 14 (5): 555–74. 
5. Jabir S, Naidu R, Azrif Bin Ahmad Annuar M et al. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. Pharmacogenomics 2012; 13 (16): 1979–88.
6. Руководство по химиотерапии опухолевых заболеваний. Под ред. Н.И.Переводчиковой, В.А.Горбуновой. 4-е изд., расшир. и доп. М: Практическая медицина, 2015. / Rukovodstvo po khimioterapii opukholevykh zabolevanii. Pod red. N.I.Perevodchikovoi, V.A.Gorbunovoi. 4-e izd., rasshir. i dop. M: Prakticheskaia meditsina, 2015. [in Russian]
7. Kus T, Aktas G, Emin Kalender M et al. Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel. OncoTargets and Therapy 2016: 9: 5073–9.
8. Tanabe Y, Hashimoto K, Shimizu C et al. Paclitaxel-induced peripheral neuropathy in patients receiving adjuvant chemotherapy for breast cancer. Int J Clin Oncol 2013; 132–8.
9. Eckhoff L, Knoop AS, Jensen MB et al. Risk of docetaxel-induced peripheral neuropathy among 1,725 Danish patients with early stage breast cancer. Breast Cancer Res Treat 2013; 142: 109–18.
10. Leskelä S, Jara C, Leandro-García LJ et al. Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity. Pharmacogenomics J 2011; 11: 121–9.
11. Корман Д.Б. Мишени и механизмы действия противоопухолевых препаратов. М.: Практическая медицина, 2014; с. 132, 135. / Korman D.B. Misheni i mekhanizmy deistviia protivoopukholevykh preparatov. M.: Prakticheskaia meditsina, 2014; s. 132, 135. [in Russian]
12. Addington J, Freimer M. Chemotherapy-induced peripheral neuropathy: an update on the current understanding [version 1; referees: 2 approved]. F1000Research 2016; 5 (F1000 Faculty Rev): 1466.
13. Mironov SL, Ivannikov MV, Johansson M. [Ca2+] i signaling between mitochondria and endoplasmic reticulum in neurons is regulated by microtubules. From mitochondrial permeability transition pore to Ca2+-induced Ca2+ release. J Biol Chem 2005; 280: 715–21.
14. Canta A, Pozzi E, Alda Carozzi V. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN). Toxics 2015; 3: 198–215.
15. Flatters SJ, Bennett GJ. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction. Pain 2006; 122 (3): 245–57.
16. Evtodienko YV, Teplova VV, Sidash SS et al. Microtubule-active drugs suppress the closure of the permeability transition pore in tumour mitochondria. FEBS Lett 1996; 39: 86–8.
17. Kidd J, Pilkington M, Schell M et al. Paclitaxel affects cytosolic Ca2+ signals by opening the mitochondrial permeability transition pore. J Biol Chem 2002; 277: 6504–10.
18. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87: 99–163.
19. Baines CP. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol 2009; 46: 850–7.
20. Carré M et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 2002; 277 (37): 33664–9. 
21. Новиков В.Е., Левченкова О.С. Митохондриальные мишени для фармакологической регуляции адаптации клетки к воздействию гипоксии. Обзоры по клинической фармакологии и лекарственной терапии. 2014; 12 (2):  28–33. / Novikov V.E., Levchenkova O.S. Mitokhondrial'nye misheni dlia farmakologicheskoi reguliatsii adaptatsii kletki k vozdeistviiu gipoksii. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii. 2014; 12 (2): 28–33. [in Russian]
22. Bernardi P, Krauskopf A, Basso E et al. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 2006; 273: 2077–99.
23. Rodi D, Janes R, Sanganee H et al. Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. J Mol Biol 1999; 285: 197–203.
24. Peters CM et al. An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat. Brain Res 2007; 1168: 46–59.
25. Jabir S, Naidu R, Azrif Bin Ahmad Annuar M et al. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. Pharmacogenomics 2012; 13 (16): 1979–88.
26. Hertz DL. Germline pharmacogenetics of paclitaxel for cancer treatment. Pharmacogenomics 2013; 14 (9): 1065–84.
27. Baker SD, Verweij J, Cusatis GA et al. Pharmacogenetic Pathway Analysis of Docetaxel Elimination. Clin Pharmacol Ther 2009; 85 (2): 155–63.
28. Li Jing. Pharmacogenomics of drug metabolizing enzymes and transporters: implications for cancer therapy. Pharmacogenomics and Personalized Medicine 2011; 11–33.
29. Bosch TM, Huitema AD, Doodeman VD et al. Pharmacogenetic screening of CYP3A and ABCB1in relation to population pharmacokinetics of docetaxel. Clin Cancer Res 2006; 5786–93.
30. Tran A, Jullien V, Alexandre J et al. Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms. Clin Pharmacol Ther 2006; 79 (6): 570–80.
31. Baker SD, Verweij J, Cusatis GA et al. Pharmacogenetic pathway analysis of docetaxel elimination. Clin Pharmacol Ther 2009; 85 (2): 155–63.
32. Gréen H, Soderkvist P, Rosenberg P et al. Pharmacogenetic studies of paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol 2009; 104 (2): 130–7.
33. Henningsson A, Marsh S, Loos WJ et al. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1polymorphisms with the pharmacokinetics of paclitaxel. Clin Cancer Res 2005; 11(22): 8097–104.
34. Bergmann TK, Brasch-Andersen C, Gréen H et al. Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.  Pharmacogenomics J 2011; 11 (2): 113–20.
35. Fransson MN, Gréen H, Litton JE, Friberg LE. Influence of Cremophor EL and genetic polymorphisms on the pharmacokinetics of paclitaxel and its metabolites using a mechanismbased model. Drug Metab Dispos 2011; 39 (2): 247–55.
36. Marsh S, Somlo G, Li X et al. Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 2007; 7 (5): 362–5.
37. Hertz DL. Roy S, Motsinger-Reif AA et al. CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol 2013; 24 (6): 1472–8.
38. Hertz DL. Motsinger-Reif AA, Drobish A et al. CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Breast Cancer Res Treat 2012; 134 (1): 401–10.
39. Abraham JE, Guo Q, Dorling L et al. 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 (9): 2466–75.
40. Rizzo R, Spaggiari F, Indelli M et al. Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients. Breast Cancer Res Treat 2010; 124 (2): 593–8.
41. Chang H, Rha SY, Jeung HC et al. Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients. Ann Oncol 2009; 20 (2): 272–7.

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1. Tiuliandin S.A., Garin A.M., Gorbunova V.A. Taksany – novye protivoopukholevye preparaty rastitel'nogo proiskhozhdeniia s unikal'nym mekhanizmom deistviia. Vestn. RONTs im. N.N.Blokhina RAMN. 1993; 4 (S): 96–101. [in Russian]
2. Korman D.B. Osnovy protivoopukholevoi khimioterapii. M: Prakticheskaia meditsina, 2006. [in Russian]
3. Roriguez-Antona C. Pharmacogenomics of paclitaxel. Pharmacogenomics 2010; 11 (5): 621–3.
4. Krens SD, McLeod HL, Hertz DL. Pharmacogenetics, enzyme probes and therapeutic drug monitoring as potential tools for individualizing taxane therapy. Pharmacogenomics 2013; 14 (5): 555–74. 
5. Jabir S, Naidu R, Azrif Bin Ahmad Annuar M et al. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. Pharmacogenomics 2012; 13 (16): 1979–88.
6. Rukovodstvo po khimioterapii opukholevykh zabolevanii. Pod red. N.I.Perevodchikovoi, V.A.Gorbunovoi. 4-e izd., rasshir. i dop. M: Prakticheskaia meditsina, 2015. [in Russian]
7. Kus T, Aktas G, Emin Kalender M et al. Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel. OncoTargets and Therapy 2016: 9: 5073–9.
8. Tanabe Y, Hashimoto K, Shimizu C et al. Paclitaxel-induced peripheral neuropathy in patients receiving adjuvant chemotherapy for breast cancer. Int J Clin Oncol 2013; 132–8.
9. Eckhoff L, Knoop AS, Jensen MB et al. Risk of docetaxel-induced peripheral neuropathy among 1,725 Danish patients with early stage breast cancer. Breast Cancer Res Treat 2013; 142: 109–18.
10. Leskelä S, Jara C, Leandro-García LJ et al. Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity. Pharmacogenomics J 2011; 11: 121–9.
11. Korman D.B. Misheni i mekhanizmy deistviia protivoopukholevykh preparatov. M.: Prakticheskaia meditsina, 2014; s. 132, 135. [in Russian]
12. Addington J, Freimer M. Chemotherapy-induced peripheral neuropathy: an update on the current understanding [version 1; referees: 2 approved]. F1000Research 2016; 5 (F1000 Faculty Rev): 1466.
13. Mironov SL, Ivannikov MV, Johansson M. [Ca2+] i signaling between mitochondria and endoplasmic reticulum in neurons is regulated by microtubules. From mitochondrial permeability transition pore to Ca2+-induced Ca2+ release. J Biol Chem 2005; 280: 715–21.
14. Canta A, Pozzi E, Alda Carozzi V. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN). Toxics 2015; 3: 198–215.
15. Flatters SJ, Bennett GJ. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction. Pain 2006; 122 (3): 245–57.
16. Evtodienko YV, Teplova VV, Sidash SS et al. Microtubule-active drugs suppress the closure of the permeability transition pore in tumour mitochondria. FEBS Lett 1996; 39: 86–8.
17. Kidd J, Pilkington M, Schell M et al. Paclitaxel affects cytosolic Ca2+ signals by opening the mitochondrial permeability transition pore. J Biol Chem 2002; 277: 6504–10.
18. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87: 99–163.
19. Baines CP. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol 2009; 46: 850–7.
20. Carré M et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 2002; 277 (37): 33664–9. 
21. Novikov V.E., Levchenkova O.S. Mitokhondrial'nye misheni dlia farmakologicheskoi reguliatsii adaptatsii kletki k vozdeistviiu gipoksii. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii. 2014; 12 (2): 28–33. [in Russian]
22. Bernardi P, Krauskopf A, Basso E et al. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 2006; 273: 2077–99.
23. Rodi D, Janes R, Sanganee H et al. Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. J Mol Biol 1999; 285: 197–203.
24. Peters CM et al. An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat. Brain Res 2007; 1168: 46–59.
25. Jabir S, Naidu R, Azrif Bin Ahmad Annuar M et al. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. Pharmacogenomics 2012; 13 (16): 1979–88.
26. Hertz DL. Germline pharmacogenetics of paclitaxel for cancer treatment. Pharmacogenomics 2013; 14 (9): 1065–84.
27. Baker SD, Verweij J, Cusatis GA et al. Pharmacogenetic Pathway Analysis of Docetaxel Elimination. Clin Pharmacol Ther 2009; 85 (2): 155–63.
28. Li Jing. Pharmacogenomics of drug metabolizing enzymes and transporters: implications for cancer therapy. Pharmacogenomics and Personalized Medicine 2011; 11–33.
29. Bosch TM, Huitema AD, Doodeman VD et al. Pharmacogenetic screening of CYP3A and ABCB1in relation to population pharmacokinetics of docetaxel. Clin Cancer Res 2006; 5786–93.
30. Tran A, Jullien V, Alexandre J et al. Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms. Clin Pharmacol Ther 2006; 79 (6): 570–80.
31. Baker SD, Verweij J, Cusatis GA et al. Pharmacogenetic pathway analysis of docetaxel elimination. Clin Pharmacol Ther 2009; 85 (2): 155–63.
32. Gréen H, Soderkvist P, Rosenberg P et al. Pharmacogenetic studies of paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol 2009; 104 (2): 130–7.
33. Henningsson A, Marsh S, Loos WJ et al. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1polymorphisms with the pharmacokinetics of paclitaxel. Clin Cancer Res 2005; 11(22): 8097–104.
34. Bergmann TK, Brasch-Andersen C, Gréen H et al. Impact of CYP2C8*3 on paclitaxelclearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.  Pharmacogenomics J 2011; 11 (2): 113–20.
35. Fransson MN, Gréen H, Litton JE, Friberg LE. Influence of Cremophor EL and genetic polymorphisms on the pharmacokinetics of paclitaxel and its metabolites using a mechanismbased model. Drug Metab Dispos 2011; 39 (2): 247–55.
36. Marsh S, Somlo G, Li X et al. Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 2007; 7 (5): 362–5.
37. Hertz DL. Roy S, Motsinger-Reif AA et al. CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol 2013; 24 (6): 1472–8.
38. Hertz DL. Motsinger-Reif AA, Drobish A et al. CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Breast Cancer Res Treat 2012; 134 (1): 401–10.
39. Abraham JE, Guo Q, Dorling L et al. 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 (9): 2466–75.
40. Rizzo R, Spaggiari F, Indelli M et al. Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients. Breast Cancer Res Treat 2010; 124 (2): 593–8.
41. Chang H, Rha SY, Jeung HC et al. Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients. Ann Oncol 2009; 20 (2): 272–7.

Л.В.Шестакова*, Д.А.Сычев, И.В.Поддубная 

ФГБОУ ДПО «Российская медицинская академия непрерывного последипломного образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1
*Lyubov_shestakova@list.ru

________________________________________________

L.V.Shestakova*, D.A.Sychev, I.V.Poddubnaya

Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1
*Lyubov_shestakova@list.ru