Lupo Gabriella, Caporarello Nunzia, Olivieri Melania, Cristaldi Martina, Motta Carla, Bramanti Vincenzo, Avola Roberto, Salmeri Mario, Nicoletti Ferdinando, Anfuso Carmelina D
Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
Front Pharmacol. 2017 Jan 6;7:519. doi: 10.3389/fphar.2016.00519. eCollection 2016.
Primary solid tumors originate close to pre-existing tissue vasculature, initially growing along such tissue blood vessels, and this phenomenon is important for the metastatic potential which frequently occurs in highly vascularized tissues. Unfortunately, preclinic and clinic anti-angiogenic approaches have not been very successful, and multiple factors have been found to contribute to toxicity and tumor resistance. Moreover, tumors can highlight intrinsic or acquired resistances, or show adaptation to the VEGF-targeted therapies. Furthermore, different mechanisms of vascularization, activation of alternative signaling pathways, and increased tumor aggressiveness make this context even more complex. On the other hand, it has to be considered that the transitional restoration of normal, not fenestrated, microvessels allows the drug to reach the tumor and act with the maximum efficiency. However, these effects are time-limited and different, depending on the various types of cancer, and clearly define a specific "normalization window." So, new horizons in the therapeutic approaches consist on the treatment of the tumor with pro- (instead of anti-) angiogenic therapies, which could strengthen a network of well-structured blood vessels that facilitate the transport of the drug.
原发性实体瘤起源于已有的组织脉管系统附近，最初沿此类组织血管生长，这种现象对于常发生于血管高度丰富组织中的转移潜能很重要。不幸的是，临床前和临床抗血管生成方法一直不太成功，并且已发现多种因素会导致毒性和肿瘤耐药性。此外，肿瘤可表现出内在或获得性耐药，或显示出对VEGF靶向治疗的适应性。此外，不同的血管生成机制、替代信号通路的激活以及肿瘤侵袭性增加，使得这种情况更加复杂。另一方面，必须考虑到正常的、非有孔的微血管的短暂恢复能使药物到达肿瘤并以最大效率发挥作用。然而，这些效应是有时间限制的，并且因癌症类型而异，明确界定了一个特定的“正常化窗口”。因此，治疗方法的新方向在于采用促血管生成（而非抗血管生成）疗法治疗肿瘤，这可以强化一个结构良好的血管网络，便于药物运输。
