Vandetanib belongs to the first generation of targeted drugs

Vandetanib is classified as a first-generation multi-target tyrosine kinase inhibitor (TKI). These drugs inhibit cancer cell proliferation and angiogenesis by blocking tumor growth signaling pathways. Vandetanib was first developed by AstraZeneca and mainly targets the three major signaling pathways of RET, EGFR and VEGFR. RET mutations play a core driving role in medullary thyroid cancer (MTC; thyroid cancer), while VEGFR inhibition helps reduce tumor angiogenesis, and EGFR blockade can further slow down the proliferation of cancer cells. This multi-target mechanism makes vandetanib one of the important breakthroughs in the field of early targeted therapy.

The first generationTKI drugs are characterized by their wide range of action and the ability to inhibit multiple signaling pathways at the same time, but they may also cause more non-target side effects. The research and development concept of vandetanib originated from the early exploration of the interaction between the tumor microenvironment and signaling networks. It has been clinically proven to delay disease progression and improve the survival and quality of life of some MTC patients. However, compared with the second- and third-generation targeted drugs developed subsequently, its target selectivity is lower, and some patients may need to change treatment options due to drug resistance or toxic reactions.

In recent years, with the development of medicine, second-generation selective RET inhibitors targeting RET mutations, such as pratinib and seputinib, have been released one after another. They are better than vandetanib in terms of specificity and tolerability. However, as a pioneer, vandetanib's clinical experience still has important reference significance, especially when there is a lack of alternative drugs or special mutant subtypes, and it is still listed as one of the treatment options in some guidelines.

From a mechanism perspective, vandetanib blocks the growth signal of medullary thyroid cancer cells by inhibiting theRET signaling pathway, which is its core mechanism of action. At the same time, VEGFR inhibits tumor angiogenesis, limiting the nutrient supply in the tumor microenvironment, thereby achieving dual anti-tumor effects. This design concept of "multi-target, combined blocking" also provides the basis for the subsequent development of multi-pathway targeted drugs.

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