Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition

Cancer Cell International

Review

Yuqian Wang¹  Changquan Ling¹  Rui Han²  Lingeng Lu³ 

[1] Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, 200433, Shanghai, P. R. China;Department of Chinese Medicine, Naval Medical University, 200433, Shanghai, P. R. China;Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, 200433, Shanghai, P. R. China;Department of Chinese Medicine, Naval Medical University, 200433, Shanghai, P. R. China;Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, P. R. China;Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, 60 College Street, 06520-8034, New Haven, CT, USA;School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, 06520-8034, New Haven, CT, USA;Yale Cancer Center, Yale University, 60 College Street, 06520-8034, New Haven, CT, USA;School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, 06520-8034, New Haven, CT, USA;Yale Cancer Center, Yale University, 60 College Street, 06520-8034, New Haven, CT, USA;

关键词: HCC;    HDAC inhibitor;    Immune therapy;    Oncotherapy sensitizer;    PD-L1 nuclear translocation;   

DOI  :  10.1186/s12935-023-03051-0

 received in 2023-06-30, accepted in 2023-09-03,  发布年份 2023

来源: Springer

【 摘 要 】

Hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 1

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