摘要
结直肠癌(CRC)是世界上最常见的癌症之一.。在过去的十年中,靶向治疗的发展给了转移性结直肠癌(mCRC)管理的一个癌症治疗新方向,并丰富了本病管理的治疗设备。在mCRC中,基于bevacizumab在临床试验中带来的最受欢迎的生存受益,通过血管内皮生长因子(VEGF)途径进行靶向的血管再生术已经引起了人们特别关注。最近,大型III期试验表明新抗血管增生药物aflibercept和regorafenib有临床效果 。然而,其它抗血管增生药物的临床前与临床研究结果却令人失望。 此外,血管增生抑制剂(AIs)在未筛选病人人群中表现出了温和这一优点。因此,深入研究预测生物标记物是必要的,但是到目前为止都失败了。然而,aflibercept和regorafenib被证明有益于bevacizumab单纯性和难治性病人,可能会反转AIs的获得性耐药性。这篇综述描述了mCRC中AIs发展的最近进展,特别关注了aflibercept和regorafenib,临床试验中这些药物评价所存在的挑战和设计发现临床有意义的生物标记物临床试验的潜在战略。
关键词: 结直肠癌,血管再生术,血管增生抑制剂,生物标记物,血管内皮生长因子(VEGF),bevacizumab
Current Drug Targets
Title:Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Volume: 18 Issue: 1
Author(s): Khurum Khan, David Cunningham, Ian Chau
Affiliation:
关键词: 结直肠癌,血管再生术,血管增生抑制剂,生物标记物,血管内皮生长因子(VEGF),bevacizumab
摘要: Colorectal cancer (CRC) is one of the commonest cancers in the world. During the last decade, the development of targeted therapies has given cancer treatment a novel direction in management of metastatic CRC (mCRC) and has enriched the therapeutic armamentarium in the management of this disease. In mCRC, targeting angiogenesis via the vascular endothelial growth factor (VEGF) pathway has been of particular interest based on the favourable survival benefit demonstrated by bevacizumab in clinical trials. More recently, large phase III studies have shown clinical efficacy for the new antiangiogenic agents aflibercept and regorafenib. However, the results of pre-clinical and clinical studies of other anti-angiogenic agents have been disappointing.
Furthermore, the benefits from angiogenic inhibitors (AIs) in an unselected patient population are modest. Research into predictive biomarkers is therefore essential, but has, to date, been unsuccessful. Nevertheless, aflibercept and regorafenib have been shown to benefit both bevacizumab naive and refractory patients, suggesting that acquired resistance to AIs can be potentially reversed. This review describes the most recent advances in development of AIs in mCRC with particular focus on aflibercept and regorafenib, the existing challenges for the evaluation of these agents in clinical practice and potential strategies in designing clinical trials that could lead to the discovery of clinically meaningful biomarkers.Export Options
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Cite this article as:
Khurum Khan, David Cunningham, Ian Chau , Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions, Current Drug Targets 2017; 18 (1) . https://dx.doi.org/10.2174/1389450116666150325231555
DOI https://dx.doi.org/10.2174/1389450116666150325231555 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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