Yi-Sian Huang1,2, Chung-Yung Ma1,2, Hsiao-Yuh Roan3, Cheng-Hsiung Chiang4, Hsiao-Hui Tsou4, Chen-Hui Chen3, Yi-Fan Lin2, Horng-Dar Wang2, Chiou-Hwa Yuh1,5,6,7,*
Oncology Research, Vol.34, No.6, 2026, DOI:10.32604/or.2026.074145
- 21 May 2026
Abstract Objectives: Hepatocellular carcinoma (HCC) arising in metabolic dysfunction–associated steatotic liver disease (MASLD) develops under lipid-rich stress and inflammatory remodeling, which can alter therapeutic windows. We aimed to determine whether phenotypic response surface–guided optimization (PRS-OPT) can nominate hepatocyte-sparing propolis–metformin–regorafenib (PMR) dose windows that retain antitumor activity under MASLD-like fatty-acid (FA) stress and translate to an in vivo immune endpoint. Methods: PMR combinations were profiled in hepatoma cell lines (PLC/PRF/5 and HepG2) and non-malignant hepatocytes (THLE-2) under FA-free and FA-enriched conditions. Quadratic response surfaces were fitted and used for constrained dose nomination, followed by in vitro validation. Cell-death contributions were… More >