Work

Development of the FGFR4-ADC bearing the ferroptosis inducer sulfasalazine for hepatocellular carcinoma

Year: 2025

Type: article

Abstract: Hepatocellular carcinoma (HCC), the most prevalent liver cancer, accounts for ∼90% of all cases. Despite antibody-drug conjugates (ADCs) showing significant efficacy in treating various hematologic malignancies and solid tumors, their application in HCC treatment is unimpressive. In this study, we identified that fibroblast growth factor receptor 4 (FGFR4) is highly expressed in HCC patient tumors and its expression correlates with overall survival rates, suggesting that FGFR4 could be an excellent therapeutic target for HCC. We subsequently developed an innovative anti-FGFR4 antibody exhibiting robust binding and endocytosis activities within HCC cells. Utilizing a GGFG linker coupled with the ferroptosis inducer sulfasalazine, we produced an FGFR4-ADC compound. This ADC specifically induced ferroptosis in FGFR4-expressing HCC cells and demonstrated FGFR4 expression-dependent anti-tumor activity in xenograft models. The preclinical pharmacokinetics and safety profile of our developed FGFR4-ADC suggest it may represent a pioneering ADC molecule offering a strategy for treating patients with tumor-associated FGFR4 expression.

Source: iScience

DOI: 10.1016/j.isci.2025.113718

Authors: Ying Zhang, Xiaohong Cui, Jing Du, Ge Cui, Yuhang Ling, Chengwu Tang

Institutions: Huzhou Normal University, Air Force Medical University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240