摘要

Tumor dormancy is the ability of cancer cells to survive in a non-proliferating state. This condition can depend on three main mechanisms: cell cycle arrest (quiescence or cell dormancy), immunosurveillance (immunologic dormancy), or lack of functional blood vessels (angiogenic dormancy). In particular, under angiogenic dormancy, cancer cell proliferation is counterbalanced by apoptosis owing to poor vascularization, impeding tumor mass expansion beyond a microscopic size, with an asymptomatic and non-metastatic state. Tumor vasculogenic or non-angiogenic switch is essential to promote escape from tumor dormancy, leading to tumor mass proliferation and metastasis. In avascular lesions angiogenesis process results blocked from the equilibrium between pro- and anti-angiogenic factors, such as vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1), respectively. The angiogenic switch mainly depends on the disruption of this balance, in favor of pro-angiogenic factors, and on the recruitment of circulating endothelial progenitors (CEPs) that promote the formation of new blood vessels. Metronomic chemotherapy, the regular intake of doses able to sustain low but active concentrations of chemotherapeutic drugs during protracted time periods, is an encouraging therapeutic approach that has shown to upregulate anti-angiogenic factors such as TSP-1 and decline pro-angiogenic factors such as VEGF, suppressing the proangiogenic cells such as CEPs. In this perspective, metronomic chemotherapy may be one of the available therapeutic approaches capable to modulate favorably the angiogenic tumor dormancy, but further research is essential to better define this particular characteristic.

译文

肿瘤休眠是癌细胞在非增殖状态下生存的能力。这种情况取决于三个主要机制: 细胞周期阻滞 (静止或细胞休眠) 、免疫监视 (免疫休眠) 或缺乏功能性血管 (血管生成休眠)。特别是，在血管生成休眠状态下，由于不良的血管化，癌细胞增殖被细胞凋亡抵消，阻碍肿瘤肿块扩张超过微观尺寸，处于无症状和非转移状态。肿瘤血管生成或非血管生成开关对于促进摆脱肿瘤休眠，导致肿瘤大量增殖和转移至关重要。在无血管病变中，血管生成过程导致促血管生成因子和抗血管生成因子之间的平衡受阻，如血管内皮生长因子 (VEGF) 和 thrombospondin-1 (TSP-1)。血管生成开关主要取决于这种平衡的破坏，有利于促血管生成因子，以及促进新血管形成的循环内皮祖细胞 (CEPs) 的募集。节拍化疗，能够在长时间内维持低但有效的化疗药物浓度的定期剂量摄入, 是一种令人鼓舞的治疗方法，已显示上调抗血管生成因子如 TSP-1，并降低促血管生成因子如 VEGF，抑制促血管生成细胞如 CEPs。从这个角度来看，节拍化疗可能是一种有效的治疗方法，能够有利地调节血管生成肿瘤的休眠，但是进一步的研究对于更好地定义这一特定特征是必要的。