Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment

• Published in: Cancer management and research Vol. 11; pp. 3847 - 3860
• Main Authors: Capozzi, Monica, De Divitiis, Chiara, Ottaiano, Alessandro, von Arx, Claudia, Scala, Stefania, Tatangelo, Fabiana, Delrio, Paolo, Tafuto, Salvatore
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2019; Dove; Dove Medical Press
• Subjects: Angiogenesis; Biological markers; Cancer treatment; Carcinoma; Diarrhea; Drug therapy; Endothelial growth factors; Endothelium; Fibroblast growth factors; Growth factors; Hepatocellular carcinoma; Hypertension; Infection; Kinases’ inhibitors; Lenvatinib; Microvessel density; Phenols (Class of compounds); Platelet-derived growth factor; Proteinuria; Renal cell carcinoma; Respiratory system agents; Review; Thyroid cancer; Thyroid diseases; Toxicity; Tumors; Tyrosine; Vascular endothelial growth factor; microvessel density; tumors; kinase inhibitors; angiogenesis
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S188316

Lenvatinib is an emerging multi-kinase inhibitor with a preferential anti-angiogenic activity, which has shown efficacy in the treatment of renal cell carcinoma, differentiated thyroid cancer and hepatocellular carcinoma. It inhibits vascular endothelial growth factor receptor family (VEGFR1-3), fibroblast growth factor receptor family (FGFR1-4), platelet-derived growth factor receptor-alpha (PDGFRα), tyrosine-kinase receptor (KIT) and rearranged during transfection receptor (RET). In this review we have evaluated the development from bench to bedside of lenvatinib. PubMed, MEDLINE and clinicaltrials.gov are the sources of data. Furthermore, the preclinical in vitro and in vivo data, as well as efficacy and toxicity results of lenvatinib in the clinic, are presented and discussed. Treatment with lenvatinib causes side effects (hypertension, proteinuria, fatigue and diarrhea), which are predominantly related to the inhibition of angiogenesis. For these reasons, the identification of biomarkers of efficacy and resistance to lenvatinib is a key challenge in order to select responsive patients. This review provides an overview on lenvatinib's clinical use, perspectives and indications for future development.