Drug Targets for Thyroid Cancer

Drug Targets for Thyroid Cancer with Approved Drug Vandetanib

Drug targets Cancer drugs Company
RETVEGFR2VEGFR3EGFR Vandetanib AstraZeneca

Vandetanib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets the rearranged during transfection receptor (RET), VEGF receptor (VEGFR2-3), and EGF receptor (EGFR), is the first systemic therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic or progressive advanced medullary thyroid cancer. In a randomized phase III trial of patients with unresectable, locally advanced, or metastatic medullary thyroid cancer, vandetanib improved progression-free survival compared with placebo. (Chau N G et al. Vandetanib for the treatment of medullary thyroid cancer[J]. Clinical Cancer Research, 2013, 19(3): 524-529.)

Drug Targets for Thyroid Cancer with Approved Drugs Cabozantibib

Drug target Cancer drugs Company
RETMETVEGFR2 Cabozantinib Exelixis Inc.

RET, MET and VEGFR2 signaling pathways are upregulated in thyroid tumors and have been implicated in the pathogenesis of Medullary thyroid cancer through promotion of proinvasive and proangiogenic phenotypes. Cabozantinib is a TKI that targets three relevant pathways in Medullary thyroid cancer: MET, VEGFR2, and RET. In a phase I study, cabozantinib demonstrated promising clinical activity in a cohort of heavily pretreated patients with Medullary thyroid cancer.

Drug Targets for Thyroid Cancer with Approved Drug Sorafenib

Drug target Cancer drugs Company
B-RAF, C-RAF, VEGFR1, VEGFR2VEGFR3PDGFRB, RET Sorafenib Bayer and Onyx Pharmaceuticals

For hereditary medullary thyroid cancer, mutations in the RET gene are essential in more than 95% of cases and are also important for the development of sporadic medullary thyroid cancer (50% of cases). Activating mutations in protein kinase B-type RAF (BRAF) kinase play a key role in the carcinogenesis of papillary thyroid cancer in up to 45% of cases, as do RAS mutations (10%), as well as rearrangements in the RET gene (RET/PTC) in 5–30% of cases. Sorafenib is the first compound capable of inhibiting all RAF kinases that are administered in clinical practice. Moreover, sorafenib targets a panel of tyrosine kinase receptors such as VEGF receptors 1–3, PDGFRB, and RET, which give sorafenib not only proapoptotic properties but also antiangiogenic effects that are of special interest in thyroid carcinomas

Drug TargetS for Thyroid Cancer with Approved Drug Lenvatinib

Drug target Cancer drugs Company
VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, PDGFRA, RET, KIT lenvatinib Eisai Co.

Although historically limited, treatment options for patients with radioiodine-refractory differentiated thyroid cancer have expanded with the advent of molecular therapies that target alterations in signalling pathways implicated in the pathogenesis and proliferation of thyroid cancer. One such pathway abnormality involves vascular endothelial growth factor (VEGF) and its receptors (VEGFRs); increased activity in this signalling network in patients with differentiated thyroid cancer is associated with aggressive and metastatic disease. Other pathway abnormalities involved in the development of thyroid cancer include those involving fibroblast growth factor (FGF) and its receptors (FGFRs), platelet-derived growth factor receptor (PDGFR), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras oncogene homolog (RAS) and rearranged during transfection proto-oncogene (RET).
Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor alpha, and RET and KIT signalling networks, which are implicated in tumour growth and maintenance. In the EU and USA, lenvatinib is indicated for the treatment of locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer.

Drug targets for Thyroid cancer: Related Information