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肽类作为潜在的抗癌药物。

Peptides as Potential Anticancer Agents.

机构信息

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, Mohali, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, Mohali, India.

出版信息

Curr Top Med Chem. 2019;19(17):1491-1511. doi: 10.2174/1568026619666190125161517.

Abstract

Cancer consists of heterogeneous multiple cell subpopulation which at a later stage develop resistant phenotypes, which include resistance to pro-apoptotic stimuli and/or cytotoxic resistance to anticancer compounds. The property of cancerous cells to affect almost any part of the body categorizes cancer to many anatomic and molecular subtypes, each requiring a particular therapeutic intervention. As several modalities are hindered in a variety of cancers and as the cancer cells accrue varied types of oncogenic mutations during their progression the most likely benefit will be obtained by a combination of therapeutic agents that might address the diverse hallmarks of cancer. Natural compounds are the backbone of cancer therapeutics owing to their property of affecting the DNA impairment and restoration mechanisms and also the gene expression modulated via several epigenetic molecular mechanisms. Bioactive peptides isolated from flora and fauna have transformed the arena of antitumour therapy and prompt progress in preclinical studies is promising. The difficulties in creating ACP rest in improving its delivery to the tumour site and it also must maintain a low toxicity profile. The substantial production costs, low selectivity and proteolytic stability of some ACP are some of the factors hindering the progress of peptide drug development. Recently, several publications have tried to edify the field with the idea of using peptides as adjuvants with established drugs for antineoplastic use. This review focuses on peptides from natural sources that precisely target tumour cells and subsequently serve as anticancer agents that are less toxic to normal tissues.

摘要

癌症由异质的多个细胞亚群组成,这些细胞亚群在后期会发展出耐药表型,包括对促凋亡刺激的抗性和/或对抗癌化合物的细胞毒性抗性。癌细胞影响身体几乎任何部位的特性将癌症分为许多解剖学和分子亚型,每种亚型都需要特定的治疗干预。由于多种治疗方法在多种癌症中受到限制,并且癌细胞在其进展过程中积累了各种致癌突变,因此最有可能通过联合治疗药物获得益处,这些药物可能针对癌症的多种标志性特征。天然化合物是癌症治疗的基础,因为它们具有影响 DNA 损伤和修复机制以及通过多种表观遗传分子机制调节基因表达的特性。从动植物中分离出的生物活性肽已经改变了抗肿瘤治疗的领域,临床前研究的迅速进展令人鼓舞。ACP 研发的难点在于提高其向肿瘤部位的递送效率,同时保持低毒性。一些 ACP 的大量生产成本、低选择性和蛋白水解稳定性是阻碍肽类药物开发进展的因素之一。最近,有几篇出版物试图用肽作为佐剂与已有的抗肿瘤药物联合使用的想法来启发该领域。这篇综述重点介绍了来自天然来源的肽,这些肽能精确靶向肿瘤细胞,随后作为抗癌药物,对正常组织的毒性较低。

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