Vandetanib and Lenvatinib for the Treatment of Thyroid Cancers

Abstract

Several drugs with Rearranged during Transfection (RET) kinase-inhibitory activity were recently introduced for thyroid cancer patients. RET gene aberrations were found in differentiated thyroid cancers and medullary thyroid cancers, subsets of thyroid cancers. Rearrangement of RET gene was found in differentiated thyroid cancers and point mutations were observed in medullary thyroid cancers, and both types of RET gene change result in the ligand-independent activation of RET kinase activity. Given the relationship of RET activity and thyroid cancers, RET inhibitors were developed as anti-tumor agents for thyroid cancers. Vandetanib, sorafenib, cabozantinib, and lenvatinib was approved drugs for thyroid cancer patients, and discovery and development processes of vandetanib and lenvatinib were discussed in this review.

Unboxing the molecular modalities of mutagens in cancer

“…Moreover, pro-inflammatory cytokines energizing intracellular RONS production (Kay et al 2019). ROS (being secondary messenger), hypoxia, and DNA damage contribute to the signaling cascade of receptors (e.g., members of the Toll-like receptors (TLRs) or nucleotidebinding oligomerization domain (NOD)-like receptors (NLRs) that instigate pro-inflammatory innate immune response through an array of functionally diverse down-stream signaling elements (e.g., NF-κB, STAT1, IRF-3, and caspase-1 activation) (Pálmai-Pallag and Bachrati 2014) also cytokines such as IL6, STAT3, and TNF-α (Kidane et al 2014). Moreover, damaged DNA leads to upregulation of IRF7 and phosphorylation of IRF3, resulting in its translocation to the nucleus from the cytoplasm, where it functions as the transcription factor.…”