Dimova Ivanka, Popivanov Georgi, Djonov Valentin
Institute of Anatomy, University of Bern, Switzerland.
J BUON. 2014 Jan-Mar;19(1):15-21.
A vast amount of data shows that angiogenesis has a pivotal role in tumor growth, progression, invasiveness and metastasis. This is a complex process involving essential signaling pathways such as vascular endothelial growth factor (VEGF) and Notch in vasculature, as well as additional players such as bone marrow-derived endothelial progenitor cells. Primary tumor cells, stromal cells and cancer stem cells strongly influence vessel growth in tumors. Better understanding of the role of the different pathways and the crosstalk between different cells during tumor angiogenesis are crucial factors for developing more effective anticancer therapies. Targeting angiogenic factors from the VEGF family has become an effective strategy to inhibit tumor growth and so far the most successful results are seen in metastatic colorectal cancer (CRC), renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLL). Despite the initial enthusiasm, the angiogenesis inhibitors showed only moderate survival benefit as monotherapy, along with a high cost and many side effects. Obviously, other important pathways may affect the angiogenic switch, among them Notch signaling pathway attracted a large interest because its ubiquitous role in carcinogenesis and angiogenesis. Herein we present the basics for VEGF and Notch signaling pathways and current advances of targeting them in antiangiogenic, antitumor therapy.
大量数据表明，血管生成在肿瘤生长、进展、侵袭和转移中起着关键作用。这是一个复杂的过程，涉及血管系统中诸如血管内皮生长因子（VEGF）和Notch等重要信号通路，以及诸如骨髓来源的内皮祖细胞等其他相关因素。原发性肿瘤细胞、基质细胞和癌症干细胞对肿瘤血管生长有强烈影响。更好地理解肿瘤血管生成过程中不同信号通路的作用以及不同细胞之间的相互作用，是开发更有效抗癌疗法的关键因素。靶向VEGF家族的血管生成因子已成为抑制肿瘤生长的有效策略，迄今为止，在转移性结直肠癌（CRC）、肾细胞癌（RCC）和非小细胞肺癌（NSCLL）中取得了最成功的结果。尽管最初人们热情高涨，但血管生成抑制剂作为单一疗法仅显示出适度的生存获益，同时成本高昂且有许多副作用。显然，其他重要信号通路可能影响血管生成开关，其中Notch信号通路因其在肿瘤发生和血管生成中的普遍作用而备受关注。在此，我们介绍VEGF和Notch信号通路的基础知识以及在抗血管生成、抗肿瘤治疗中靶向它们的当前进展。
