Regorafenib

The process of angiogenesis is a complex balance of positive and negative regulators, and vascular endothelial growth factor (VEGF) is one of the most important proangiogenic factors involved in tumor angiogenesis. One of the drugs targeting this process is regorafenib, a multi-kinase inhibitor. It inhibits VEGF receptors 1, 2, and 3; rearranged during transfection (RET); receptor tyrosine kinase (KIT); platelet-derived growth factor receptor (PDGFR) alpha and beta; fibroblast growth factor receptor (FGFR) 1 and 2; angiopoietin-1 receptor (Tie2); discoidin domain-containing receptor 2 (DDR2); Ephrin type-A receptor 2 (Eph 2A); tropomyosin receptor kinase A (TrkA); rapidly accelerated fibrosarcoma (RAF-1); v-RAF murine sarcoma viral oncogene homolog B1 (BRAF); stress-activated protein kinase-2 (SAPK2); protein tyrosine kinase 5 (PTK5); and Abelson murine leukemia virus (Abl). Regorafenib has been approved for patients with metastatic colorectal cancer (CRC), locally advanced or metastatic gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (HCC). We present a review of regorafenib which includes the history, basic chemistry, pharmacology, pharmacokinetics, clinical indications, drug interactions, and safety profile. We performed a search in PubMed and other sources using the search terms “CRC,” “GIST,” “HCC,” “osteosarcoma,” and “regorafenib” and searched for full-text articles published in the past 10 years. Out of the total 65 studies identified, we included 46 studies. We combined all the abstracts and conference proceedings to generate a comprehensive review.