Nuffield Division of Laboratory Science, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
Cancer Rep (Hoboken). 2022 Dec;5(12):e1318. doi: 10.1002/cnr2.1318. Epub 2020 Dec 9.
The concept that all the tumors need the formation of new vessels to grow inspired the hypothesis that inhibition of angiogenesis would have led to "cure" cancer. The expectancy that this type of therapy would have avoided the insurgence of resistance was based on the concept that targeting normal vessels, instead of the cancer cells which easily develop new mutations, would have allowed evasion of drug caused selection is, however, more complex as it was made apparent by the discovery of nonangiogenic tumors. At the same time an increasing number of trials with antiangiogenic drugs were coming out as not as successful as expected, mostly because of the appearance of unexpected resistance.
Among the several different mechanisms of resistance to antiangiogenic treatment by now described, we review the evidences that vascular co-option and vasculogenic mimicry by nonangiogenic tumors are effectively two of such mechanisms. We focused on reviewing exclusively the study, both clinical and preclinical, that offer a demonstration that vascular co-option and vasculogenic mimicry are effectively two mechanisms of both intrinsic and acquired resistance.
The discovery that vascular co-opting and vasculogenic mimicry are two ways of escaping antiangiogenic treatment, prompts the need for a better understanding of this phenomenon in order to improve cancer treatment.
所有肿瘤都需要新血管形成才能生长的观点启发了这样一种假设，即抑制血管生成将导致“治愈”癌症。这种治疗方法有望避免耐药性的产生，其依据是靶向正常血管（而不是容易产生新突变的癌细胞）将避免药物选择导致的逃逸，然而，随着非血管生成肿瘤的发现，这种情况变得更加复杂。与此同时，越来越多的抗血管生成药物试验并没有像预期的那样成功，主要是因为出现了意想不到的耐药性。
在目前描述的几种不同的抗血管生成治疗耐药机制中，我们回顾了证据，表明血管选择和非血管生成肿瘤的血管生成模拟实际上是其中两种机制。我们专门重点回顾了仅提供证据表明血管选择和血管生成模拟实际上是内在和获得性耐药的两种机制的临床前和临床研究。
发现血管选择和血管生成模拟是逃避抗血管生成治疗的两种方式，这促使人们需要更好地了解这一现象，以改善癌症治疗。
