Imatinib treatment for gastrointestinal stromal tumour (GIST).
Imatinib treatment for gastrointestinal stromal tumour (GIST).
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DOI：
10.1111/j.1582-4934.2009.00983.x
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发表时间：
2010-01
影响因子：
5.3
通讯作者：
Bacchi CE
中科院分区：
文献类型：
--
作者：
Lopes LF;Bacchi CE
胃肠道间质瘤（GIST）是胃肠道最常见的间叶性肿瘤。GIST被认为起源于Cajal的胰岛细胞（胃肠道的起搏细胞）或相关干细胞，并且以KIT或血小板衍生生长因子受体α（PDGFRA）激活突变为特征。伊马替尼的使用彻底改变了GIST的管理，改变了其自然史，大大提高了许多患者的生存时间，延缓了疾病进展。伊马替尼在控制晚期胃肠道间质瘤方面的成功引起了人们对该药物的新辅助和辅助使用的兴趣。推荐使用伊马替尼的新辅助（术前），以通过减小肿瘤大小来促进切除并避免毁损手术，并且辅助治疗适用于复发风险高的患者。GIST的分子表征（基因分型）已成为疾病常规管理的重要组成部分，因为KIT和PDGFRA突变状态可预测伊马替尼缓解的可能性。然而，绝大多数最初对伊马替尼有反应的患者将发生肿瘤进展（继发性耐药）。继发性耐药通常与干扰药物结合的继发性KIT或PDGFRA突变有关。多种新型酪氨酸激酶抑制剂可能对伊马替尼耐药GIST的治疗有潜在的作用，因为它们干扰KIT和PDGFRA受体或下游信号蛋白。
Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.
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影响因子：
3.7
作者：
Agaram, Narasimhan P.;Wong, Grace C.;Guo, Tianhua;Maki, Robert G.;Singer, Samuel;DeMatteo, Ronald P.;Besmer, Peter;Antonescu, Cristina R.
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45.3
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3.7
作者：
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通讯作者：
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影响因子：
7.3
作者：
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通讯作者：
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