Arizona Cancer Center, University of Arizona, Tucson AZ, 85724, USA.
Recent Pat Anticancer Drug Discov. 2010 Jun;5(2):99-108. doi: 10.2174/157489210790936252.
Cell penetrating peptides (CPPs) are 9-35mer cationic and/or amphipathic peptides that are rapidly internalized across cell membranes. Importantly, they can be linked to a variety of cargo, including anti-cancer therapeutics, making CPPs an efficient, effective and non-toxic mechanism for drug delivery. In this review, we discuss a number of CPP conjugated therapies (CTTs) that are either patented are in the progress of patenting, and show strong promise for clinical efficacy. The CTTs discussed here target a number of different processes specific to cancer progression, including proliferation, survival and migration. In addition, many of these CTTs also increase sensitivity to current anti-cancer therapy modalities, including radiation and other DNA damaging chemotherapies, thereby decreasing the toxic dosage required for effective treatment. Mechanistically, these CTTs function in a dominant-negative manner by blocking tumor-specific protein-protein interactions with the CPP-conjugated peptide or protein. The treatment of both cell lines and mouse models demonstrates that this method of molecular targeting results in equal if not greater efficacy than current standards of care, including DNA damaging agents and topoisomerase inhibitors. For the treatment of invasive carcinoma, these CTTs have significant clinical potential to deliver highly targeted therapies without sacrificing the patient's quality of life.
细胞穿透肽(CPPs)是 9-35 个氨基酸组成的阳离子肽和/或两亲肽,可快速穿过细胞膜进入细胞内。重要的是,它们可以与多种货物(包括抗癌治疗药物)连接,使 CPP 成为一种高效、有效且无毒的药物递送机制。在这篇综述中,我们讨论了一些已获得专利或正在申请专利的 CPP 缀合疗法(CTT),它们具有很强的临床疗效潜力。这里讨论的 CTT 针对癌症进展过程中的许多不同的特定过程,包括增殖、存活和迁移。此外,这些 CTT 中的许多还增加了对当前抗癌治疗方式(包括放射治疗和其他 DNA 损伤化疗)的敏感性,从而降低了有效治疗所需的毒性剂量。从机制上讲,这些 CTT 通过 CPP 缀合肽或蛋白阻断肿瘤特异性蛋白-蛋白相互作用,以显性负性方式发挥作用。细胞系和小鼠模型的治疗表明,这种分子靶向方法的疗效与目前的治疗标准(包括 DNA 损伤剂和拓扑异构酶抑制剂)相当,甚至更好。对于侵袭性癌的治疗,这些 CTT 具有显著的临床潜力,可以提供高度靶向的治疗,而不会牺牲患者的生活质量。