Pinto Mauricio P, Sotomayor Paula, Carrasco-Avino Gonzalo, Corvalan Alejandro H, Owen Gareth I
Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Center for Integrative Medicine and Innovative Science, Facultad de Medicina, Universidad Andrés Bello, Santiago 8370071, Chile.
Int J Mol Sci. 2016 Sep 6;17(9):1489. doi: 10.3390/ijms17091489.
Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.
肿瘤血管生成被广泛认为是“癌症的标志”之一。因此，在过去几十年中，商业血管生成抑制剂的开发和测试一直是基础癌症研究和临床癌症研究的核心焦点。虽然抗血管生成药物现已纳入标准临床实践，但与所有癌症治疗一样，肿瘤最终可能会通过采用各种策略在治疗攻击时获取营养和氧气而产生耐药性。在此，我们详细集中并综述抗血管生成治疗逃逸的三个主要机制：（1）血管生成补偿/替代途径的上调；（2）血管生成拟态；（3）血管共生。我们认为，了解癌细胞如何适应抗血管生成治疗也可能与新兴肿瘤和导致残留疾病的孤立转移细胞所采用的机制相似。最后，我们推测了使抗血管生成治疗适用于未来临床应用的策略。
