Compensatory angiogenesis and tumor refractoriness.
Compensatory angiogenesis and tumor refractoriness.
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DOI：
10.1038/oncsis.2015.14
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发表时间：
2015-06-01
期刊：
影响因子：
6.2
通讯作者：
Gacche RN
中科院分区：
文献类型：
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作者：
Gacche RN
自从将肿瘤血管生成确立为治疗靶点以来，人们对开发抗血管生成药物产生了兴趣，从而产生了针对血管内皮生长因子（VEGF）的人源化单克隆抗体（贝伐珠单抗）：血管内皮生长因子是招募血管生成的关键因素。过去三十年血管生成领域的研究也发明了一系列针对VEGF信号轴的新型有效的抗血管生成药物。尽管抗血管生成治疗具有明显的临床益处，但当前治疗环境的临床前和临床数据清楚地表明，在停止抗血管生成治疗后，其疗效短暂，肿瘤进展恢复，肿瘤侵袭性复发。因此，这种治疗方案对提高患者总体生存率的效果在临床上一直令人失望。肿瘤血管生成的病理生理学以及相关的分子和细胞基础的最新进展归因于代偿性血管生成途径的共谋，赋予肿瘤对抗血管生成药物的逃避性和内在抗性。了解这些通路在 VEGF 阻断期间如何功能性地相互影响以维持肿瘤血管生成至关重要，并且可能作为设计新治疗策略的基本先决条件，以对抗肿瘤对抗血管生成药物日益增长的傲慢态度。本综述提供了关于在细胞和分子水平上运作的主要代偿性血管生成途径及其抗血管生成药物耐药性的属性的讨论，以及针对肿瘤血管生成的未来设置的战略意见。
Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF): a key factor in recruiting angiogenesis. The past three decades' research in the area of angiogenesis also invented a series of novel and effective anti-angiogenic agents targeting the VEGF signaling axis. Despite the demonstrable clinical benefits of anti-angiogenic therapy, the preclinical and clinical data of the current therapeutic settings clearly indicate the transient efficacy, restoration of tumor progression and aggressive recurrence of tumor invasion after the withdrawal of anti-angiogenic therapy. Therefore, the impact of this therapeutic regime on improving overall survival of patients has been disappointing in clinic. The recent advances in pathophysiology of tumor angiogenesis and related molecular and cellular underpinnings attributed the conspiracy of compensatory angiogenic pathways in conferring evasive and intrinsic tumor resistance to anti-angiogenic agents. The understandings of how these pathways functionally cross-talk for sustaining tumor angiogenesis during VEGF blockade is essential and perhaps may act as a basic prerequisite for designing novel therapeutic strategies to combat the growing arrogance of tumors toward anti-angiogenic agents. The present review offers a discourse on major compensatory angiogenic pathways operating at cellular and molecular levels and their attributes with resistance to anti-angiogenic agents along with strategic opinions on future setting in targeting tumor angiogenesis.