Drug intelligence / Profile preview

ascorbic acid + sorafenib (Thomas Jefferson University)

Development stage
Unknown
Lead developer
Thomas Jefferson University
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

This combination therapy involves high-dose intravenous ascorbic acid (Vitamin C) administered in conjunction with sorafenib for the treatment of metastatic hepatocellular carcinoma. Investigated in a Phase I/II clinical trial (NCT04033107) sponsored by Thomas Jefferson University, the regimen utilizes pharmacologic doses of ascorbic acid (75 grams) to act as a pro-oxidant. At these concentrations, ascorbic acid generates hydrogen peroxide, which selectively induces oxidative stress and apoptosis in cancer cells. Sorafenib is a multi-kinase inhibitor that targets the Raf/MEK/ERK pathway and receptor tyrosine kinases involved in angiogenesis, such as VEGFR and PDGFR. Preclinical studies suggest that the combination of these two agents results in synergistic anti-tumor activity through the dysregulation of cellular calcium homeostasis and mitochondrial dysfunction, potentially enhancing the efficacy of the standard-of-care sorafenib in patients with advanced liver cancer.

Brand names
Nexavar
Other names
IV Vitamin C + sorafenibhigh-dose intravenous ascorbic acid + sorafenibascorbic acid and sorafenib
02

Targets

BRAF (B-Raf proto-oncogene, serine/threonine kinase)KIT (c-KIT proto-oncogene receptor tyrosine kinase)VEGFR2 (Vascular endothelial growth factor receptor 2)PDGFRB (Platelet-derived growth factor receptor beta)RAF1 (c-Raf-1 (Y340D/Y341D))VEGFR3 (Vascular endothelial growth factor receptor 3)FLT3 (Fms related receptor tyrosine kinase 3)

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