Advanced or Metastatic Pancreatic Cancer: Molecular Targeted Therapies
Advanced or Metastatic Pancreatic Cancer: Molecular Targeted Therapies
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DOI：
10.1002/msj.20217
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发表时间：
2010-11-01
影响因子：
--
通讯作者：
Rocha-Lima, Caio M.
中科院分区：
文献类型：
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作者：
Bayraktar, Soley;Rocha-Lima, Caio M.
胰腺癌患者通常表现为晚期疾病，这种疾病是致命的，并且众所周知难以治疗。然而，过去十年的临床发展是温和的，进展最多是渐进的。在胰腺腺癌的所有情况下，辅助、局部晚期和转移性的核心药物和治疗支柱仍然是吉西他滨。过去十年的研究最初集中在细胞毒性疗法与吉西他滨的组合，并且在此期间已经发表了大量的研究，其目的在于靶向与胰腺肿瘤生长、侵袭、转移、血管生成和抗凋亡有关的分子异常。该研究特别重要，因为数据表明，大量的遗传改变只影响胰腺肿瘤发生中涉及的几个主要信号通路和过程。迄今为止，只有厄洛替尼（一种表皮生长因子受体酪氨酸激酶抑制剂）在III期临床试验中与吉西他滨组合显示出边际生存益处。尽管靶向治疗在临床环境中的失败令人沮丧，可以合理地推测，随着胰腺癌分子生物学的不断解开，将会取得重大进展。这篇综述描述了已在临床试验中测试的胰腺癌的一些重要发展和靶向药物Mt Sinai J Med 77606-619，2010（C）2010西奈山学校医学
Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat However, clinical developments over the past decade have been modest and advances are incremental at most The core drug and the backbone of treatment in all settings of pancreatic adenocarcinoma-adjuvant, locally advanced, and metastatic remains gemcitabine The past decade of research focused initially on combining cytotoxic therapies with gemcitabine, and during that time a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis, and resistance to apoptosis This research is of particular importance, as data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated marginal survival benefit in combination with gemcitabine in phase III clinical trials Even though the failures of targeted therapies in the clinical setting are discouraging, it is reasonable to surmise that major progress will evolve as the molecular biology of pancreatic adenocarcinoma continues to be unraveled This review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials Mt Sinai J Med 77606-619, 2010(C)2010 Mount Sinai School Medicine