Research Programs Unit, Translational Cancer Biology, Biomedicum Helsinki 1, University of Helsinki., Haartmaninkatu 8, 00014 Helsinki, Finland.
Research Programs Unit, Translational Cancer Biology, Biomedicum Helsinki 1, University of Helsinki., Haartmaninkatu 8, 00014 Helsinki, Finland.
Bioorg Med Chem. 2018 Jun 1;26(10):2797-2806. doi: 10.1016/j.bmc.2017.08.052. Epub 2017 Sep 1.
Accounting for 16 million new cases and 9 million deaths annually, cancer leaves a great number of patients helpless. It is a complex disease and still a major challenge for the scientific and medical communities. The efficacy of conventional chemotherapies is often poor and patients suffer from off-target effects. Each neoplasm exhibits molecular signatures - sometimes in a patient specific manner - that may completely differ from the organ of origin, may be expressed in markedly higher amounts and/or in different location compared to the normal tissue. Although adding layers of complexity in the understanding of cancer biology, this cancer-specific signature provides an opportunity to develop targeting agents for early detection, diagnosis, and therapeutics. Chimeric antibodies, recombinant proteins or synthetic polypeptides have emerged as excellent candidates for specific homing to peripheral and central nervous system cancers. Specifically, peptide ligands benefit from their small size, easy and affordable production, high specificity, and remarkable flexibility regarding their sequence and conjugation possibilities. Coupled to imaging agents, chemotherapies and/or nanocarriers they have shown to increase the on-site delivery, thus allowing better tumor mass contouring in imaging and increased efficacy of the chemotherapies associated with reduced adverse effects. Therefore, some of the peptides alone or in combination have been tested in clinical trials to treat patients. Peptides have been well-tolerated and shown absence of toxicity. This review aims to offer a view on tumor targeting peptides that are either derived from natural peptide ligands or identified using phage display screening. We also include examples of peptides targeting the high-grade malignant tumors of the central nervous system as an example of the complex therapeutic management due to the tumor's location. Peptide vaccines are outside of the scope of this review.
癌症每年导致 1600 万新发病例和 900 万人死亡，使许多患者束手无策。它是一种复杂的疾病，仍然是科学界和医学界的主要挑战。传统化疗的疗效往往不佳，患者会遭受脱靶效应的影响。每个肿瘤都表现出分子特征——有时以患者特异性的方式——这些特征可能与起源器官完全不同，其表达量可能明显更高，或者与正常组织相比在不同的位置表达。尽管这给癌症生物学的理解增加了复杂性，但这种肿瘤特异性特征为开发早期检测、诊断和治疗的靶向药物提供了机会。嵌合抗体、重组蛋白或合成多肽已成为针对外周和中枢神经系统癌症的特异性归巢的优秀候选物。具体来说，肽配体具有以下优点：其分子量小、易于生产且价格低廉、特异性高，并且在序列和缀合可能性方面具有显著的灵活性。与成像剂、化疗药物和/或纳米载体结合使用，它们已被证明可以增加原位递药，从而改善成像中的肿瘤轮廓，并提高与不良反应减少相关的化疗疗效。因此，一些肽单独或组合在一起已在临床试验中用于治疗患者。肽的耐受性良好，且无毒性。本综述旨在提供对源自天然肽配体或通过噬菌体展示筛选鉴定的肿瘤靶向肽的看法。我们还包括了靶向中枢神经系统高级别恶性肿瘤的肽的示例，作为由于肿瘤位置导致的复杂治疗管理的一个例子。肽疫苗不在本综述范围内。
