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PEP06(TB01)与曲氟尿苷/替匹嘧啶(TAS-102)联合应用于人大肠癌异种移植模型中的抗癌作用。

Anticancer effects of PEP06 (TB01) in combination with Trifluridine/Tipiracil (TAS-102) in a xenograft model of human colorectal cancer.

作者信息

Lin Ruohong, Cheng Jiaxing, Zhao Jinlong, Zhou Liang, Li Jian, Yang Xinchun

机构信息

Zhuhai Tengbai Pharmaceutical Co., Ltd, Zhuhai, 519031, China.

State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

出版信息

J Cancer Res Clin Oncol. 2024 Dec 26;151(1):22. doi: 10.1007/s00432-024-05984-z.

DOI:10.1007/s00432-024-05984-z
PMID:39724415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11671547/
Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most common cancer globally, with advanced stages presenting significant treatment challenges. Recently years, drug combination therapy has become a promising strategy for cancer treatment.

OBJECTIVE

To evaluate the therapeutic efficacy of the combination of the anti-angiogenic drug PEP06 (TB01) and the cytotoxic drug Trifluridine/Tipiracil (TAS-102) in human CRC HCT-116 xenograft mouse model. And quantitative assessment of the interaction between TB01 and TAS-102 in the treatment based on pharmacological effects.

METHODS

This study utilized the human CRC HCT-116 xenograft nude mouse model to evaluate the antitumor effects of TAS-102 and TB01, both as mono-therapies and in combination therapies.

RESULTS

The combination therapy not only demonstrated significantly inhibited tumor growth in a dose-dependent manner, but also seems to reduce the common toxicity associated with such treatments, as shown by the maintenance of body weights in the treated mice.

CONCLUSION

The synergistic effect observed from the combined use of TAS-102 and TB01 suggests a promising new treatment avenue for refractory CRC patients, meriting further investigation and potential clinical application.

摘要

背景

结直肠癌(CRC)是全球第三大常见癌症,晚期阶段面临重大治疗挑战。近年来,联合药物治疗已成为一种有前景的癌症治疗策略。

目的

评估抗血管生成药物PEP06(TB01)与细胞毒性药物曲氟尿苷/替匹嘧啶(TAS-102)联合使用对人CRC HCT-116异种移植小鼠模型的治疗效果。并基于药理作用对TB01和TAS-102在治疗中的相互作用进行定量评估。

方法

本研究利用人CRC HCT-116异种移植裸鼠模型评估TAS-102和TB01单药治疗及联合治疗的抗肿瘤效果。

结果

联合治疗不仅以剂量依赖性方式显著抑制肿瘤生长,而且似乎降低了此类治疗相关的常见毒性,如治疗小鼠体重维持所示。

结论

TAS-102和TB01联合使用所观察到的协同效应为难治性CRC患者提供了一条有前景的新治疗途径,值得进一步研究和潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/58b2c6c015ef/432_2024_5984_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/7a7d487e0708/432_2024_5984_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/9eab02615c75/432_2024_5984_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/863a5c1fd3bb/432_2024_5984_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/1ba152bb3631/432_2024_5984_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/58b2c6c015ef/432_2024_5984_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/7a7d487e0708/432_2024_5984_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/9eab02615c75/432_2024_5984_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/863a5c1fd3bb/432_2024_5984_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/1ba152bb3631/432_2024_5984_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0497/11671547/58b2c6c015ef/432_2024_5984_Fig5_HTML.jpg

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本文引用的文献

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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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替吉奥胶囊联合贝伐珠单抗作为三线治疗晚期或复发性结直肠癌的疗效观察:一项Ⅱ期、多中心临床试验(TAS-CC4 研究)。
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HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/-catenin signaling activation.HYD-PEP06通过抑制PI3K/AKT和WNT/β-连环蛋白信号激活来抑制肝细胞癌转移、上皮-间质转化及癌症干细胞样特性。
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