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胰腺癌化学预防的作用机制和药物靶点

Mechanisms and Drug Targets for Pancreatic Cancer Chemoprevention.

机构信息

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.

University of Colorado Cancer Center, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.

出版信息

Curr Med Chem. 2018;25(22):2545-2565. doi: 10.2174/0929867324666170320120647.

Abstract

BACKGROUND

Pancreatic cancer management remains a major challenge to society. Poor prognosis results in dismal patient survival rates and quality of life post chemo/radiation therapies. Although progress has been made in drug development for targeting pancreatic cancer, accompanying issues of drug resistance renders it futile. While intake of fruits and vegetables in routine diets has been linked to reduced risk of pancreatic cancer, a wide variety of natural agents are being evaluated as adjuvant therapies in combination with frontline chemotherapeutics in pancreatic cancer clinical trials.

OBJECTIVE

This review highlights the emerging area of cancer chemoprevention with natural/ dietary compounds serving as novel agents possessing strong anticancer properties; these are pleiotropic agents targeting multiple pathways with minimal toxicity in normal tissue.

METHODS

We employed extensive literature search and considered all the relevant information presented in a concise, well-balanced and structured format.

RESULTS

Completed and ongoing human studies with natural agents have shown surprisingly successful rates for regulating pancreatic carcinogenesis. Combinatorial therapies with synthetic, approved drugs and natural agents not only improved the patient response rates, but also helped in overcoming drug resistance and inducing chemosensitivity to the resistant tumors, as opposed to monotherapies for pancreatic cancer chemoprevention.

CONCLUSION

The current review focuses on the available chemotherapeutic drugs and their limitations, and moves on to discuss the wide realm of chemopreventive efficacy that the natural agents have to offer. It discusses the underlying mechanisms of action and available information, from extensive literature analysis, to highlight the novelty of these agents for their antitumor effects against pancreatic cancer.

摘要

背景

胰腺癌的治疗仍然是社会面临的重大挑战。由于预后不良,患者的生存率和化疗/放疗后的生活质量都很低。尽管在针对胰腺癌的药物开发方面已经取得了进展,但随之而来的耐药问题使得这些药物的开发变得徒劳无益。虽然常规饮食中摄入水果和蔬菜与降低胰腺癌风险有关,但在胰腺癌临床试验中,人们正在评估各种天然药物作为辅助疗法与一线化疗药物联合使用。

目的

本文综述了天然/膳食化合物作为具有强大抗癌特性的新型药物在癌症化学预防方面的新兴领域;这些药物是多效性药物,可靶向多种途径,对正常组织的毒性最小。

方法

我们进行了广泛的文献检索,并以简洁、平衡和结构化的格式考虑了所有相关信息。

结果

已完成和正在进行的天然药物人体研究表明,调节胰腺癌发生的成功率非常高。与合成的、已批准的药物和天然药物联合进行的组合疗法不仅提高了患者的反应率,而且有助于克服耐药性并诱导耐药肿瘤的化疗敏感性,而不是针对胰腺癌化学预防的单一疗法。

结论

本综述重点讨论了现有的化疗药物及其局限性,然后讨论了天然药物提供的广泛化学预防效果领域。它讨论了作用机制和现有信息,从广泛的文献分析中,强调了这些药物作为抗肿瘤药物针对胰腺癌的新颖性。

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