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结直肠癌中上皮-间质转化的药物靶点。

Pharmacological Targeting of Epithelial-to-Mesenchymal Transition in Colorectal Cancer.

机构信息

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Curr Pharm Des. 2022;28(28):2298-2311. doi: 10.2174/1381612828666220728152350.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most common cause of cancer deaths, and metastasis is a major cause of mortalities. The survival rate of patients diagnosed with metastasis remains disappointing. Therefore, the prevention of tumor dissemination as well as treatment of existing metastatic lesions is an important focus of new cancer therapies. Epithelial-to-mesenchymal transition (EMT) is defined as a cellular transition from an epithelial to a mesenchymal state and determines lethal cancer characteristics consisting of invasiveness, metastasis formation, and drug resistance.

METHODS

We reviewed PubMed and EMBASE libraries to collect data about pharmacological targeting of Epithelial- to-Mesenchymal Transition in colorectal cancer to prevent metastatic tumor distribution and improve the survival of patients with CRC.

RESULTS

We provided an overview of the available EMT-based therapies in CRC, summarized FDA-approved and under-clinical trial drugs with EMT-inhibiting properties in metastatic CRC, and described several agents preventing EMT-associated progression and metastasis in preclinical studies. Although various preclinical and clinical findings have proven that inhibiting EMT via different pharmacological approaches can reduce aggressive features of many cancers, not all agents possessing EMT-inhibiting function in preclinical research exhibit improvement in clinical studies.

CONCLUSION

Combating EMT as a therapeutic intervention with the aim of preventing tumor dissemination, eliminating exiting metastasis, and promoting resistance to therapy may be a novel and effective strategy in the treatment of CRC. We hope that further exploration of EMT-related mechanisms and EMT-inhibiting drugs will provide more opportunities to treat CRC efficiently.

摘要

背景

结直肠癌(CRC)是癌症死亡的第三大常见原因,转移是导致死亡的主要原因。转移性疾病患者的生存率仍然令人失望。因此,预防肿瘤扩散以及治疗现有的转移性病变是癌症新疗法的一个重要重点。上皮-间质转化(EMT)被定义为上皮细胞向间充质状态的细胞转变,并决定了侵袭性、转移形成和耐药性等致命的癌症特征。

方法

我们检索了 PubMed 和 EMBASE 数据库,以收集关于结直肠癌中 EMT 靶向药理学以预防转移性肿瘤分布和改善 CRC 患者生存的相关数据。

结果

我们概述了 CRC 中现有的 EMT 相关疗法,总结了 FDA 批准的和临床试验阶段的具有 EMT 抑制特性的转移性 CRC 药物,并描述了几种在临床前研究中预防 EMT 相关进展和转移的药物。尽管各种临床前和临床研究都证明了通过不同的药理学方法抑制 EMT 可以降低许多癌症的侵袭性特征,但并非所有在临床前研究中具有 EMT 抑制功能的药物在临床研究中都能改善疗效。

结论

将 EMT 作为一种治疗干预手段,旨在预防肿瘤扩散、消除现有的转移灶,并促进对治疗的耐药性,可能是 CRC 治疗的一种新的有效策略。我们希望进一步探索 EMT 相关机制和 EMT 抑制药物将为有效治疗 CRC 提供更多机会。

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