What does Vandetanib not target?

Vandetanib is a typical multi-target tyrosine kinase inhibitor that has been widely studied and used in the treatment of medullary thyroid cancer (thyroid cancer). It can simultaneously inhibit the activity of multiple receptor tyrosine kinases, includingEGFR (epidermal growth factor receptor), VEGFR (vascular endothelial growth factor receptor) family, RET (rearranged oncogene), BRK, TIE2, and some EPH receptors and Src family members. Through this mechanism, vandetanib can not only directly inhibit the proliferation of tumor cells, but also block the angiogenesis process and improve the tumor microenvironment, thereby delaying tumor progression.

However, not all targets related to tumor development are within its inhibitory range. Vandetanib does not directly act on molecules such as the mTOR pathway, PI3K/AKT signaling, ALK fusion proteins, and BRAF mutations, which means that its efficacy is limited in some tumor types dominated by driver genes. This is why vandetanib is mainly concentrated in the field of medullary thyroid cancer and has not been widely expanded to cancer types such as lung cancer or melanoma that are centered on other molecular pathways.

In in vitro studies, the N-desmethyl metabolite of vandetanib accounted for 7% to 17% of the total exposure. This metabolite also has inhibitory effects on VEGF receptors (KDR, Flt-1) and EGFR, and maintains similar activity to the parent drug, which provides support for the persistence of its efficacy. Even so, its activity is mainly concentrated on the above-mentioned types of receptors, and does not involve immune checkpoints (such as PD-1/PD-L1), DNA repair-related proteins or the PARP pathway. Therefore, other drugs are still needed to make up for the shortcomings of the mechanism in combination therapy.

With the development of precision medicine, doctors will strictly screen patients when using vandetanib to ensure that their tumor-driving mechanisms are consistent with the drug targets to maximize efficacy. For molecular targets that are not included in its scope of action, it needs to be used in combination with other targeted drugs or immunotherapy.

Reference materials:https://www.drugs.com/caprelsa.html