Please wait a minute...
Journal of ZheJiang University(Medical Science)  2015, Vol. 44 Issue (5): 473-478    DOI: 10.3785/j.issn.1008-9292.2015.09.01
    
Research progress in toxicology of molecular targeted anticancer drugs
LOU Xiao-e, CHEN Min, YANG Bo
Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou 310058, China
Download:   PDF(696KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Objective:Drug therapy is essential for cancer treatment. The molecular targeted anticancer drugs develop rapidly in recent years, since the effectiveness of traditional chemotherapy is unsatisfactory and the adverse reactions are high. However, molecular targeted anticancer drugs would damage the function of heart, liver or lung, and may cause adverse effects such as hand-foot syndrome, which restrains their clinical application. Therefore, it is critical for pharmaceutical toxicology to study the toxicity, the related mechanisms and the preventive measures of molecular targeted anticancer drugs.



Key wordsAntineoplastic agents/toxicity      Protein-tyrosine kinases/antagonists &      inhibitors      Protein-tyrosine kinases/adverse effects      Heart/drug effects      Liver/drug effects      Lung/drug effects      Skin diseases/etiology      Review     
Received: 28 May 2015     
CLC:  R96  
Cite this article:

LOU Xiao-e, CHEN Min, YANG Bo. Research progress in toxicology of molecular targeted anticancer drugs. Journal of ZheJiang University(Medical Science), 2015, 44(5): 473-478.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2015.09.01     OR     http://www.zjujournals.com/xueshu/med/Y2015/V44/I5/473


分子靶向抗肿瘤药物的毒性研究进展

目的:药物治疗是肿瘤治疗的重要手段,传统的化疗药物疗效欠佳、副作用大,因此以酪氨酸激酶抑制剂为代表的分子靶向抗肿瘤药物得到大力发展。分子靶向抗肿瘤药物具有靶向性强、疗效显著等特点,但在临床应用的过程中会对心、肝、肺等重要脏器造成不同程度的损伤以及引发手足综合征等不良反应,极大地限制其在临床的应用和发展。因此,分析分子靶向抗肿瘤药物的毒性反应临床现状,研究其作用机制及保护干预措施已成为药物毒理学研究的重要任务。


关键词: 抗肿瘤药/毒性,  蛋白酪氨酸激酶类/拮抗剂和抑制剂,  蛋白酪氨酸激酶类/副作用,  心脏/药物作用,  肝/药物作用,  肺/药物作用,  皮肤疾病,  综述 
[[1]]   DASSONVILLE O, BOZEC A, FISCHEL J L, et al. EGFR targeting therapies:monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences[J]. Crit Rev Oncol Hemat, 2007,62(1):53-61.
[[2]]   ZHANG S, LIU X, BAWA-KHALFE T,et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity[J]. Nat Med, 2012,18(11):1639-1942.
[[3]]   RASCHI E, VASINA V, URSINO M G, et al. Anticancer drugs and cardiotoxicity:insights and perspectives in the era of targeted therapy[J]. J Pharmacol Exp Ther, 2010,125(2):196-218.
[[4]]   OLSON E M, ABDEL-RASOUL M, MALY J, et al. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab[J]. Ann Oncol, 2013,24(6):1526-1533.
[[5]]   ATALLAH E, DURAND J B, KANTARJIAN H, et al. Congestive heart failure is a rare event in patients receiving imatinib therapy[J]. Blood, 2007,110(4):1233-1237.
[[6]]   FRANCIS J, AHLUWALIA M S, WETZLER M, et al. Reversible cardiotoxicity with tyrosine kinase inhibitors[J]. Clin Adv Hematol Oncol, 2010,8(2):128-132.
[[7]]   ORPHANOS G S, IOANNIDIS G N, ARDAVANIS A G. Cardiotoxicity induced by tyrosine kinase inhibitors[J]. Acta Oncol, 2009,48(7):964-970.
[[8]]   SCHMIDINGER M, ZIELINSKI C C, VOGL U M, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma[J]. J Clin Oncol,2008,26(32):5204-5212.
[[9]]   AI D, BANCHS J, OWUSU-AGYEMANG P, et al. Chemotherapy induced cardiovascular toxicity:beyond anthracyclines[J]. Minerva Anestesiol, 2014,80(5):586-594.
[[10]]   DOHERTY K R, WAPPEL R L, TALBERT D R, et al. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes[J]. Toxicol Appl Pharm, 2013,272(1):245-255.
[[11]]   TRUONG J, YAN A T, CRAMAROSSA G, et al. Chemotherapy-induced cardiotoxicity:detection, prevention and management[J]. Can J Cardiol, 2014,30(8):869-878.
[[12]]   ALBINI A, PENNESI G, DONATELLI F, et al. Cardiotoxicity of anticancer drugs:the need for cardio-oncology and cardio-oncological prevention[J]. J Natl Cancer Inst, 2010,102(1):14-25.
[[13]]   FERRERO D, POGLIANI E M, REGE-CAMBRIN G, et al. Corticosteroids can reverse severe imatinib-induced hepatotoxicity[J]. Haematologica, 2006,91(6 Suppl):ECR27.
[[14]]   REA D, BERGERON A, FIESCHI C, et al. Dasatinib-induced lupus[J]. Lancet, 2008,372(9640):713-714.
[[15]]   SCHAID D J, SPRAGGS C F, MCDONNELL S K, et al. Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury[J]. J Clin Oncol, 2014,32(22):2296-2303.
[[16]]   YANO Y, NAMBA Y, MORI M, et al. Treatment of non-small-cell lung cancer with erlotinib following gefitinib-induced hepatotoxicity:review of 8 clinical cases[J]. Lung Cancer Int, 2012,2012:354657.
[[17]]   MANCUSO A, ZAVAGLIA C, BAI F, et al. Letter:sorafenib hepatotoxicity may be enhanced during treatment of advanced hepatocellular carcinoma in HIV-infected patients[J]. Aliment Pharm Therap, 2013,38(11-12):1414-1416.
[[18]]   SHAH R R, MORGANROTH J, SHAH D R. Hepatotoxicity of tyrosine kinase inhibitors:clinical and regulatory perspectives[J]. Drug Safety, 2013,36(7):491-503.
[[19]]   BISSELL D M, GORES G J, LASKIN D L, et al. Drug-induced liver injury:mechanisms and test systems[J]. Hepatology, 2001,33(4):1009-1013.
[[20]]   DU K, WILLIAMS C D, MCGILL M R, et al. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation[J]. Toxicol Appl Pharm, 2013,273(3):484-491.
[[21]]   IKEDA T. Idiosyncratic drug hepatotoxicity:strategy for prevention and proposed mechanism[J]. Curr Med Chem, 2014,22(4):528-537.
[[22]]   DAHELE M, SENAN S. The role of stereotactic ablative radiotherapy for early-stage and oligometastatic non-small cell lung cancer:evidence for changing paradigms[J]. Cancer Res Treat, 2011,43(2):75-82.
[[23]]   CHOI M K, HONG J Y, CHANG W J, et al. A phase Ⅱ trial of gefitinib monotherapy in pretreated patients with advanced non-small cell lung cancer not harboring activating EGFR mutations:implications of sensitive EGFR mutation test[J]. Cancer Chemoth Pharm, 2015,75(6):1229-1236.
[[24]]   HERBST R S,PRAGER D, HERMANN R,et al. TRIBUTE:a phase Ⅲtrial of erlotinib hydrochloride(OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer[J]. J Clin Oncol, 2005,23(25):5892-5899.
[[25]]   YAMAGUCHI T, SEKI T, MIYASAKA C, et al. Interstitial pneumonia induced by sorafenib in a patient with hepatocellular carcinoma:an autopsy case report[J]. Oncol Lett, 2015,9(4):1633-1636.
[[26]]   HARTMANN J T, KOLLMANNSBERGER C, CASCORBI I, et al. A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer[J]. Invest New Drug, 2013,31(3):661-668.
[[27]]   CARRILLO GARCÍA C. Role of growth/differentiation factor(GDF) 15 in the regulation of embryonic neural precursors[D]. Heidelberg:Ruperto-carola University of Heidelberg, 2008.
[[28]]   SINGH S, SHI T, DUFFIN R, et al. Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO 2:role of the specific surface area and of surface methylation of the particles[J]. Toxicol Appl Pharm, 2007,222(2):141-151.
[[29]]   ZUEHLKE R L. Erythematous eruption of the palms and soles associated with mitotane therapy[J]. Dermatologica, 1974,148(2):90-92.
[[30]]   SIL A, DAS N K.Sorafenib-induced hand-foot syndrome in a patient of renal cell carcinoma[J]. Indian J Pharmacol, 2014,46(3):334-336.
[[31]]   EDESA W A, ABDELMALEK R R. Efficacy and toxicity of sunitinib in metastatic renal cell carcinoma patients in Egypt[J]. Asian Pac J Cancer P, 2015,16(5):1971-1976.
[[32]]   WANG G S. Conjecture about hand-foot syndrome in CLASSIC Trial[J]. Iran J Public Health, 2014,43(4):534-534.
[[33]]   LIN E H, CURLEY S A, CRANE C C, et al. Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer:potential benefits and COX-2 as the common mediator in pain, toxicities and survival[J]. Am J Clin Oncol Canc, 2006,29(3):232-239.
[[34]]   CARONIA D, MARTIN M, SASTRE J, et al. A polymorphism in the cytidinedeaminase promoter predicts severe capecitabine-induced hand-foot syndrome[J]. Clin Cancer Res, 2011,17(7):2006-2013.
[[35]]   YAMAMOTO D, YAMAMOTO C, IWASE S, et al. Efficacy of vitamin E treatment for hand-foot syndrome in patients receiving capecitabine[J]. Breast Care, 2010,5(6):415-416.
[[36]]   BRAIK T, YIM B, EVANS A T, et al. Randomized trial of vitamin B6 for preventing hand-foot syndrome from capecitabine chemotherapy[J]. J Community Support Oncol, 2014,12(2):65-70.
[1] ZHENG Yanrong,ZHANG Xiangnan,CHEN Zhong. Research progress on mechanism of Nix-mediated mitophagy[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 92-96.
[2] LI Wenlong,QU Haibin. Application progress on near infrared spectroscopy in quality control and process monitoring of traditional Chinese medicine[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 80-88.
[3] GAO Siqian,SHEN Yongmei,GENG Funeng,LI Yanhua,GAO Jianqing. Research progress on the animal models and treatment strategies of diabetic foot ulcer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 97-105.
[4] WANG Ying,WANG Yi,CHEN Zhong. The role of central cholinergic system in epilepsy[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 15-21.
[5] GAO Siqian,SHEN Yongmei,GENG Funeng,Yanhua LI,Jianqing GAO. Temporal lobe epilepsy and adult hippocampal neurogenesis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 97-105.
[6] LI Tongyu, LIANG Ping. Research progress on disease models and gene therapy of Duchenne muscular dystrophy[J]. Journal of ZheJiang University(Medical Science), 2016, 45(6): 648-654.
[7] FENG Sheng, CHEN Jijun, ZHENG Yichun. Research progress on the effect of glucocorticoid receptor signaling pathways in bladder cancer[J]. Journal of ZheJiang University(Medical Science), 2016, 45(6): 655-660.
[8] CAO Peng, LENG Dongjin, LI Ying, ZHANG Ziwei, LIU Lei, LI Xiaoyan. Progress on anti-tumor molecular mechanisms of dihydroartemisinin[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 501-507.
[9] LI Tingting, KE Yuehai, CHENG Hongqiang. Reasearch progress on the role of neutrophils in asthma[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 544-549.
[10] WANG Xue, ZHANG Yuchuan, CHEN Wei. Research progress on the role of TANK-binding kinase 1 in anti-virus innate immune response[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 550-557.
[11] HE Bin, CHAI Yanlan, WANG Tao, ZHOU Zhenxing, LIU Zi. Progress on clinical application of bevacizumab for the treatment of refractory cervical cancer[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 395-402.
[12] LI Xueying, ZHU Lixia, YE Xiujin. Aberrant DNA methylation and its targeted therapy in acute myeloid leukemia[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 387-394.
[13] ZHU Tianhong, ZHANG Xinmei. Research progress on the role of epithelial-mesenchymal transition in pathogenesis of endometriosis[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 439-445.
[14] DU Miaomiao, MA Gaigai, SHI Yuping. Research progress on pharmacotherapy of calcific aortic valve disease[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 432-438.
[15] SHEN Yinzhong, LU Hongzhou. Pre-exposure prophylaxis for HIV: clinical practice and challenge[J]. Journal of ZheJiang University(Medical Science), 2016, 45(3): 221-227.