Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Front Immunol. 2020 Oct 29;11:584903. doi: 10.3389/fimmu.2020.584903. eCollection 2020.
Neoangiogenesis is a recognized hallmark of cancer, granting tumor cells to dispose of metabolic substrates through a newly created vascular supply. Neoangiogenesis was also confirmed in melanoma, where vascular proliferation is associated with increased aggressiveness and poorer prognosis. Furthermore, melanoma cells show the so-called vascular mimicry, consisting in the assumption of endothelial-like features inducing the expression of pro-angiogenic receptors and ligands, which take part in the interplay with extracellular matrix (ECM) components and are potentiated by the ECM remodeling and the barrier molecule junction alterations that characterize the metastatic phase. Although neoangiogenesis was biologically proven and clinically associated with worse outcomes in melanoma patients, in the past anti-angiogenic therapies were employed with poor improvement of the already unsatisfactory results associated with chemotherapic agents. Among the novel therapies of melanoma, immunotherapy has led to previously unexpected outcomes of treatment, yet there is a still strong need for potentiating the results, possibly by new regimens of combination therapies. Molecular models in many cancer types showed mutual influences between immune responses and vascular normalization. Recently, clinical trials are investigating the efficacy of the association between anti-angiogenetic agents and immune-checkpoint inhibitors to treat advanced stage melanoma. This paper reviews the biological bases of angiogenesis in melanoma and summarizes the currently available clinical data on the use of anti-angiogenetic compounds in melanoma.
新生血管形成是癌症公认的标志之一，使肿瘤细胞能够通过新形成的血管供应来处理代谢底物。新生血管形成也在黑色素瘤中得到证实，其中血管增殖与侵袭性增加和预后不良相关。此外，黑色素瘤细胞表现出所谓的血管模拟现象，即假设具有内皮样特征，诱导促血管生成受体和配体的表达，参与与细胞外基质 (ECM) 成分的相互作用，并通过 ECM 重塑和特征转移阶段的屏障分子连接改变而增强。尽管新生血管形成在生物学上已得到证实，并与黑色素瘤患者的预后不良相关，但过去的抗血管生成治疗效果不佳，与化疗药物相关的结果仍不尽如人意。在黑色素瘤的新型治疗方法中，免疫疗法带来了以前意想不到的治疗效果，但仍强烈需要通过新的联合治疗方案来增强治疗效果。许多癌症类型的分子模型显示免疫反应和血管正常化之间存在相互影响。最近，临床试验正在研究抗血管生成剂和免疫检查点抑制剂联合治疗晚期黑色素瘤的疗效。本文综述了黑色素瘤中血管生成的生物学基础，并总结了目前关于抗血管生成化合物在黑色素瘤中的应用的临床数据。
