The vasculature is a key player and regulatory component in the multicellular microenvironment of solid tumors and, consequently, a therapeutic target. In colorectal carcinoma (CRC), antiangiogenic treatment was approved almost 20 years ago, but there are still no valid predictors of response. In addition, treatment resistance has become a problem. Vascular heterogeneity and plasticity due to species-, organ-, and milieu-dependent phenotypic and functional differences of blood vascular cells reduced the hope of being able to apply a standard approach of antiangiogenic therapy to all patients. In addition, the pathological vasculature in CRC is characterized by heterogeneous perfusion, impaired barrier function, immunosuppressive endothelial cell anergy, and metabolic competition-induced microenvironmental stress. Only recently, angiocrine proteins have been identified that are specifically released from vascular cells and can regulate tumor initiation and progression in an autocrine and paracrine manner. In this review, we summarize the history and current strategies for applying antiangiogenic treatment and discuss the associated challenges and opportunities, including normalizing the tumor vasculature, modulating milieu-dependent vascular heterogeneity, and targeting functions of angiocrine proteins. These new strategies could open perspectives for future vascular-targeted and patient-tailored therapy selection in CRC.
血管系统是实体瘤多细胞微环境中的关键参与者和调节成分，因而成为重要的治疗靶点。在结直肠癌治疗领域，抗血管生成疗法虽已获批近二十年，但至今仍缺乏有效的疗效预测指标。与此同时，治疗耐药性问题日益凸显。由于血管细胞存在物种、器官及微环境依赖性的表型和功能差异，导致血管异质性和可塑性显著，这使得针对所有患者采用标准化抗血管生成治疗方案的前景变得渺茫。此外，结直肠癌的病理性血管系统具有灌注异质性、屏障功能受损、免疫抑制性内皮细胞失能以及代谢竞争诱导的微环境应激等特征。直到近期研究才发现，血管细胞特异性分泌的血管分泌蛋白能够通过自分泌和旁分泌方式调控肿瘤的发生与发展。本综述系统梳理了抗血管生成治疗的历史沿革与现行策略，深入探讨了相关挑战与机遇，包括肿瘤血管正常化、微环境依赖性血管异质性调控以及血管分泌蛋白功能靶向等新兴方向。这些创新策略有望为未来结直肠癌血管靶向治疗及个体化治疗方案选择开辟新视野。
Blood Vessel-Targeted Therapy in Colorectal Cancer: Current Strategies and Future Perspectives
肿瘤(癌症)患者之家