f Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; [email protected] Correspondence: [email protected]; Tel.: +81-4-7133-Simple Summary: Anti-VEGFR therapy has become a mainstay of treatment for thyroid cancer across histological subtypes. However, the inhibition of this pathway is associated with unique adverse effects, some of which are life-threatening and could lead to the withdrawal of definitive remedy. To reduce this risk, the physician will have to recognize the traits of these adverse effects, which includes their timing and frequency, and adopt proper countermeasures. Moreover, management should a lot more broadly encompass the appropriate subject selection for this therapy, as well as modification from the remedy schedule and consideration of option therapies for those individuals harboring a threat of toxicity. Abstract: Recent advances inside the development of multitarget tyrosine kinase inhibitors (MTKIs), which mostly target the vascular endothelial growth aspect receptor (VEGFR), have improved prognoses and dramatically changed the treatment technique for advanced thyroid cancer. On the other hand, adverse events associated to this inhibition can interrupt therapy and from time to time bring about discontinuation. Also, they are able to be annoying and potentially jeopardize the subjects’ high quality of life, even enabling that the clinical outcome of sufferers with sophisticated thyroid cancer remains limited. Within this assessment, we summarize the prospective mechanisms underlying these adverse events (hypertension, proteinuria and renal impairment, hemorrhage, fistula formation/gastrointestinal perforation, wound healing, cardiovascular toxicities, hematological toxicity, diarrhea, fatigue, and acute cholecystitis), their traits, and actual management. In addition, we also go over the importance of connected variables, such as alternative remedies that target other pathways, the necessity of topic selection for safer administration, and patient education. Keywords: thyroid cancer; vascular endothelial growth issue; tyrosine kinase inhibitor; adverse eventAcademic Editor: Vasyl Vasko Received: 17 ERRĪ± manufacturer August 2021 Accepted: 29 October 2021 Published: 4 NovemberCitation: Enokida, T.; Tahara, M. Management of VEGFR-Targeted TKI for Thyroid Cancer. Cancers 2021, 13, 5536. doi.org/10.3390/ cancers1. Introduction Thyroid cancer is the most prevalent endocrine cancer worldwide. Presently, four multitarget tyrosine kinase inhibitors (comprising sorafenib [1,2], Lenvatinib [3,4] vandetanib [5,6], and cabozantinib [7,8]) (MTKIs) are licensed as vital therapeutic alternatives for the treatment of thyroid cancer, and have enhanced the progression-free survival (PFS) of individuals in clinical trials and real-world research. These compounds show activity against many receptor tyrosine kinases (RTKs), some involved within the pathogenesis of thyroid cancer (i.e., BRAF, RAS, RET) and other people inside the vascular angiogenic pathway (i.e., VEGFR2, platelet-derived development aspect (PDGFR)). These latter kinases–the major pro-angiogenic molecules in thyroid cancer–act by advertising the formation of a vast network of blood vessels. Accordingly, damaging the feeding blood vessels, specifically vascular endothelium, appears to be by far the most critical mechanism of action of your MTKIs in thyroid cancer. As these MTKIs are usually Caspase 4 drug employed as chronic therapies, it is crucial to successfully manage and decrease their tox