Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future

Author:

Li Junfang1ORCID,Wang Xiaodong1,Zhang Honghua1ORCID,Hu Xiaoling1,Peng Xue2ORCID,Jiang Weifan34,Zhuo Linsheng23,Peng Yan2,Zeng Guo3,Wang Zhen23

Affiliation:

1. School of Pharmacy Lanzhou University Lanzhou Gansu China

2. School of Pharmaceutical Science, Hengyang Medical School University of South China Hengyang Hunan China

3. Postdoctoral Station for Basic Medicine, School of Basic Medicine, Hengyang Medical School University of South China Hengyang Hunan China

4. The Affiliated Nanhua Hospital, Hengyang Medical School University of South China Hengyang Hunan China

Abstract

AbstractFenamates as classical nonsteroidal anti‐inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo‐preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/β‐catenin, TGF‐β, p38 MAPK, and NF‐κB pathway, and the regulation of the expressions of Sp, EGR‐1, NAG‐1, ATF‐3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.

Publisher

Wiley

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