Tucker Gordon C
Institut de Recherches Servier, Cancer Drug Discovery, 125 Chemin de Ronde, 78290 Croissy sur Seine, France.
Curr Oncol Rep. 2006 Mar;8(2):96-103. doi: 10.1007/s11912-006-0043-3.
Integrins are cell surface adhesion molecules coupling the extracellular environment to the cytoskeleton as well as receptors for transmitting signals important for cell migration, invasion, proliferation, and survival. At least six integrin inhibitors are being evaluated in clinical trials for cancer. Currently, patients with melanoma and glioblastoma multiforme benefit from Vitaxin (MedImmune, Gaithersburg, MD) or cilengitide treatment, respectively. Many phase II trials are being or have been conducted with these two compounds (the most advanced). Surprisingly, despite the broad theoretical impact of such molecules on integrin function, and thus on pathology, the clear identification of discrete clinical niches for their use remains to be defined. Possible reasons for this are discussed in this review. The parallel development of integrin antagonists as imaging tools for patient selection may accelerate the discovery of new avenues for their use.
整合素是细胞表面黏附分子，可将细胞外环境与细胞骨架连接起来，也是传递对细胞迁移、侵袭、增殖和存活至关重要信号的受体。目前至少有六种整合素抑制剂正在癌症临床试验中进行评估。目前，黑色素瘤患者和多形性胶质母细胞瘤患者分别从Vitaxin（MedImmune公司，马里兰州盖瑟斯堡）或西仑吉肽治疗中获益。目前正在或已经针对这两种化合物（最先进的）开展了许多II期试验。令人惊讶的是，尽管这类分子对整合素功能进而对病理学具有广泛的理论影响，但对于其明确的临床应用细分领域仍有待确定。本综述讨论了其中可能的原因。整合素拮抗剂作为患者选择成像工具的平行开发可能会加速其新应用途径的发现。
