Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, 430030, China.
Oncogene. 2023 Nov;42(45):3303-3318. doi: 10.1038/s41388-023-02861-w. Epub 2023 Oct 13.
MYC, a major oncogenic transcription factor, regulates target genes involved in various pathways such as cell proliferation, metabolism and immune evasion, playing a critical role in the tumor initiation and development in multiple types of cancer. In liver cancer, MYC and its signaling pathways undergo significant changes, exerting a profound impact on liver cancer progression, including tumor proliferation, metastasis, dedifferentiation, metabolism, immune microenvironment, and resistance to comprehensive therapies. This makes MYC an appealing target, despite it being previously considered an undruggable protein. In this review, we discuss the role and mechanisms of MYC in liver physiology, chronic liver diseases, hepatocarcinogenesis, and liver cancer progression, providing a theoretical basis for targeting MYC as an ideal therapeutic target for liver cancer. We also summarize and prospect the strategies for targeting MYC, including direct and indirect approaches to abolish the oncogenic function of MYC in liver cancer.
MYC 是一种主要的致癌转录因子，调节参与多种途径的靶基因，如细胞增殖、代谢和免疫逃逸，在多种类型的癌症的肿瘤发生和发展中发挥关键作用。在肝癌中，MYC 及其信号通路发生显著变化，对肝癌的进展产生深远影响，包括肿瘤增殖、转移、去分化、代谢、免疫微环境以及对综合治疗的耐药性。这使得 MYC 成为一个有吸引力的靶点，尽管它之前被认为是一种不可成药的蛋白质。在这篇综述中，我们讨论了 MYC 在肝生理、慢性肝病、肝癌发生和肝癌进展中的作用和机制，为靶向 MYC 作为肝癌理想治疗靶点提供了理论依据。我们还总结和展望了靶向 MYC 的策略，包括直接和间接方法来消除 MYC 在肝癌中的致癌功能。
