Molecular mechanisms of chemoresistance in osteosarcoma (Review).
Molecular mechanisms of chemoresistance in osteosarcoma (Review).
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骨肉瘤化疗耐药的分子机制（综述）。
DOI：
10.3892/ol.2014.1935
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发表时间：
2014-05
期刊：
影响因子：
2.9
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
He H;Ni J;Huang J
由于辅助和新辅助化疗的出现，骨肉瘤（OS）局限性病变患者的生存率得到了极大的提高。然而，这一生存率在过去30年中保持不变，患有转移性或复发性疾病的OS患者的长期生存率仍然很差。在一定程度上，这背后的原因可能归因于抗OS治疗的化学抗性。OS中的化疗耐药性似乎是由许多机制介导的，这些机制包括细胞内药物蓄积减少、药物失活、DNA修复增强、信号转导通路的扰动、凋亡和自噬相关的化疗耐药性、microRNA（miRNA）失调和癌症干细胞（CSC）介导的耐药性。此外，采用规避这些耐药机制的方法已被证明是有效的治疗OS。然而，目前几乎所有的研究在OS的耐药机制都处于起步阶段。今后的研究重点应放在以下几个方面：i）通过新的给药模式提高疗效; ii）提高对调控OS细胞增殖和生长的信号转导途径的认识; iii）阐明OS细胞自噬的信号转导途径及其与凋亡的关系; iv）利用高通量miRNA表达分析来鉴定与OS中的化学抗性相关的miRNA;以及v）鉴定CSCs在肿瘤转移中所起的作用，并深入研究OS的CSCs中的化学抗性机制。
Due to the emergence of adjuvant and neoadjuvant chemotherapy, the survival rate has been greatly improved in osteosarcoma (OS) patients with localized disease. However, this survival rate has remained unchanged over the past 30 years, and the long-term survival rate for OS patients with metastatic or recurrent disease remains poor. To a certain extent, the reason behind this may be ascribed to the chemoresistance to anti-OS therapy. Chemoresistance in OS appears to be mediated by numerous mechanisms, which include decreased intracellular drug accumulation, drug inactivation, enhanced DNA repair, perturbations in signal transduction pathways, apoptosis- and autophagy-related chemoresistance, microRNA (miRNA) dysregulation and cancer stem cell (CSC)-mediated drug resistance. In addition, methods employed to circumvent these resistance mechanism have been shown to be effective in the treatment of OS. However, almost all the current studies on the mechanisms of chemoresistance in OS are in their infancy. Further studies are required to focus on the following aspects: i) Improving the delivery of efficacy through novel delivery patterns; ii) improving the understanding of the signal transduction pathways that regulate the proliferation and growth of OS cells; iii) elucidating the signaling pathways of autophagy and its association with apoptosis in OS cells; iv) utilizing high-throughput miRNA expression analysis to identify miRNAs associated with chemoresistance in OS; and v) identifying the role that CSCs play in tumor metastasis and in-depth study of the mechanism of chemoresistance in the CSCs of OS.
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影响因子：
2.4
作者：
Coupienne, Isabelle;Fettweis, Gregory;Piette, Jacques
通讯作者：
Piette, Jacques
影响因子：
11.5
作者：
Chitnis, Meenali M.;Yuen, John S. P.;Macaulay, Valentine M.
通讯作者：
Macaulay, Valentine M.
DOI：
10.1038/tpj.2011.33
发表时间：
2012-12
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Biason P;Hattinger CM;Innocenti F;Talamini R;Alberghini M;Scotlandi K;Zanusso C;Serra M;Toffoli G
通讯作者：
Toffoli G
影响因子：
5.6
作者：
Di Fiore, Riccardo;Santulli, Andrea;Vento, Renza
通讯作者：
Vento, Renza
DOI：
10.2165/00148581-200810050-00005
发表时间：
2008-01-01
期刊：
Paediatric drugs
影响因子：
--
作者：
Chou, Alexander J;Geller, David S;Gorlick, Richard
通讯作者：
Gorlick, Richard