title: Regorafenib in metastatic colorectal cancer.
abstract: Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in the regulation of tumor angiogenesis (VEGFR1, 2, 3; angiopoietin-1 receptor), oncogenesis (stem cell growth factor receptor; RET; BRAF including BRAFV600E), and tumor microenvironment (PDGFR-β and FGFR). Based on data from the Phase III CORRECT study, regorafenib stands as a further option for patient affected by metastatic colorectal cancer who have exhausted previous available therapies. Its multi-targeted effect might explain activity in advanced lines of treatment, when cancer cells have been heavily challenged with previous lines of therapy and potentially developed multiple mechanisms of resistance, but also makes difficult to identify predictive biomarkers. In this article we examine preclinical as well as clinical data of regorafenib in the therapy of metastatic colorectal cancer, challenges for potential markers of efficacy and its role in the treatment algorithm.
authors.affiliation: Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sartore-Bianchi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zeppellini
authors.forename: Alessio
authors.initials: A
authors.lastname: Amatu
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ricotta
authors.forename: Katia
authors.initials: K
authors.lastname: Bencardino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009362:Neoplasm Metastasis; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib