sorafenib + tamoxifen

Sorafenib + tamoxifen is an investigational combination therapy consisting of two small molecule drugs, sorafenib and tamoxifen. Sorafenib is a multikinase inhibitor that targets several kinases involved in tumor cell proliferation and angiogenesis, including RAF kinases, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor beta (PDGFRB), KIT, FLT3, RET, and FGFR1. Tamoxifen is a selective estrogen receptor modulator (SERM) that acts primarily as an antagonist of the estrogen receptor in breast tissue. The combination has been studied primarily for its potential to overcome resistance to endocrine therapy in hormone receptor-positive breast cancer and has also been explored in advanced hepatocellular carcinoma. Preclinical studies suggest that sorafenib may resensitize tamoxifen-resistant breast cancer cells by reducing total and phosphorylated estrogen receptor alpha levels as well as affecting ER-associated proteins such as FOXA1 and AIB1[1][4][6]. Early clinical data indicate manageable toxicity with promising efficacy signals such as stable disease or restored sensitivity to hormone therapy[2]. This combination remains investigational.