Department of Molecular & Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Cells. 2021 Oct 27;10(11):2908. doi: 10.3390/cells10112908.
Peptides are increasingly being developed for use as therapeutics to treat many ailments, including cancer. Therapeutic peptides have the advantages of target specificity and low toxicity. The anticancer effects of a peptide can be the direct result of the peptide binding its intended target, or the peptide may be conjugated to a chemotherapy drug or radionuclide and used to target the agent to cancer cells. Peptides can be targeted to proteins on the cell surface, where the peptide-protein interaction can initiate internalization of the complex, or the peptide can be designed to directly cross the cell membrane. Peptides can induce cell death by numerous mechanisms including membrane disruption and subsequent necrosis, apoptosis, tumor angiogenesis inhibition, immune regulation, disruption of cell signaling pathways, cell cycle regulation, DNA repair pathways, or cell death pathways. Although using peptides as therapeutics has many advantages, peptides have the disadvantage of being easily degraded by proteases once administered and, depending on the mode of administration, often have difficulty being adsorbed into the blood stream. In this review, we discuss strategies recently developed to overcome these obstacles of peptide delivery and bioavailability. In addition, we present many examples of peptides developed to fight cancer.
肽类越来越多地被开发为治疗多种疾病的治疗剂,包括癌症。治疗肽具有靶向特异性和低毒性的优点。肽的抗癌作用可以直接归因于肽与其预期靶标的结合,或者肽可以与化疗药物或放射性核素缀合,并用于将药物靶向癌细胞。肽可以针对细胞表面的蛋白质,其中肽-蛋白质相互作用可以启动复合物的内化,或者肽可以设计为直接穿过细胞膜。肽可以通过多种机制诱导细胞死亡,包括膜破坏和随后的坏死、凋亡、肿瘤血管生成抑制、免疫调节、细胞信号通路的破坏、细胞周期调节、DNA 修复途径或细胞死亡途径。尽管使用肽作为治疗剂具有许多优点,但肽一旦给药就容易被蛋白酶降解,并且根据给药方式,往往难以被吸收到血液中。在这篇综述中,我们讨论了最近开发的克服肽传递和生物利用度障碍的策略。此外,我们还介绍了许多用于对抗癌症的肽类开发的例子。