D'Onofrio Nunzia, Caraglia Michele, Grimaldi Anna, Marfella Raffaele, Servillo Luigi, Paolisso Giuseppe, Balestrieri Maria Luisa
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via L. de Crecchio 7, 80138 Naples, Italy.
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy.
Biochim Biophys Acta. 2014 Aug;1846(1):1-12. doi: 10.1016/j.bbcan.2014.03.004. Epub 2014 Apr 1.
The vasculature of each organ expresses distinct molecular signatures critically influenced by the pathological status. The heterogeneous profile of the vascular beds has been successfully unveiled by the in vivo phage display, a high-throughput tool for mapping normal, diseased, and tumor vasculature. Specific challenges of this growing field are targeted therapies against cancer and cardiovascular diseases, as well as novel bioimaging diagnostic tools. Tumor vasculature-homing peptides have been extensively evaluated in several preclinical and clinical studies both as targeted-therapy and diagnosis. To date, results from several Phase I and II trials have been reported and many other trials are currently ongoing or recruiting patients. In this review, advances in the identification of novel peptide ligands and their corresponding receptors on tumor endothelium through the in vivo phage display technology are discussed. Emphasis is given to recent findings in the clinical setting of vascular-homing peptides selected by in vivo phage display for the treatment of advanced malignancies and their altered vascular beds.
每个器官的脉管系统都表达出受病理状态严重影响的独特分子特征。通过体内噬菌体展示这一用于绘制正常、患病和肿瘤脉管系统图谱的高通量工具，已成功揭示了血管床的异质性特征。这一不断发展的领域面临的特定挑战包括针对癌症和心血管疾病的靶向治疗，以及新型生物成像诊断工具。肿瘤血管归巢肽已在多项临床前和临床研究中作为靶向治疗和诊断手段进行了广泛评估。迄今为止，已报告了多项I期和II期试验的结果，许多其他试验正在进行或正在招募患者。在这篇综述中，将讨论通过体内噬菌体展示技术鉴定肿瘤内皮上新型肽配体及其相应受体方面的进展。重点介绍通过体内噬菌体展示筛选出的血管归巢肽在治疗晚期恶性肿瘤及其改变的血管床的临床应用中的最新发现。
