整合素α6靶向的肿瘤成像和治疗研究进展

Integrin α6-Targeted Molecular Imaging and Targeted Therapy in Tumors: A Research Progress

摘要: 整合素是介导细胞粘附和信号传导的重要受体超家族，在肿瘤的发生、侵袭、转移及治疗耐药中发挥关键作用，是肿瘤诊疗的重要靶点。既往研究多聚焦于整合素αvβ3和αvβ5，但其临床转化效果有限。近年来，整合素α6因在多种恶性肿瘤中显著高表达，与不良预后密切相关，且作为重要的肿瘤干细胞标志物，成为极具潜力的新兴诊疗靶点。基于靶向肽RWY及其优化衍生物，研究者已开发出覆盖正电子发射断层扫描(PET)、单光子发射计算机断层扫描(SPECT)、磁共振成像(MRI)及近红外荧光(NIRF)系列的多模态分子探针。其中，SPECT探针^99mTc-RWY已成功用于乳腺癌患者的首次人体成像，验证了该靶点的临床转化可行性。在治疗层面，功能阻断抗体、肽–药物偶联物(PDC)及纳米递药系统等策略在临床前模型中均展现出显著抗肿瘤活性。本文系统综述整合素α6靶向分子影像与治疗领域的最新进展，并展望以放射性核素偶联药物(RDC)为导向的诊疗一体化前景。

Abstract: Integrins are a major superfamily of transmembrane receptors that mediate cell adhesion and signal transduction. They play critical roles in tumor development, invasion, metastasis, and therapeutic resistance, making them attractive targets for cancer diagnosis and treatment. Previous studies have primarily focused on integrins αvβ3 and αvβ5; however, their clinical translation has achieved limited success. In recent years, integrin α6 has emerged as a promising theranostic target because of its marked overexpression in multiple malignancies, its strong association with poor prognosis, and its role as a cancer stem cell marker. Based on the integrin α6-targeted peptide RWY and its optimized derivatives, a series of multimodal molecular probes have been developed for positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and near-infrared fluorescence imaging (NIRF). Among them, the SPECT probe ^99mTc-RWY has been successfully applied in a first-in-human imaging study of breast cancer. At the therapeutic level, strategies such as function-blocking antibodies, peptide-drug conjugates (PDCs), and nano-drug delivery systems have demonstrated significant antitumor efficacy in preclinical models. This review systematically summarizes the latest advances in integrin α6-targeted molecular imaging and therapy, and discusses the future prospects of theranostics guided by radiolabeled drug conjugates (RDCs).