The relationship between vandetanib and cabozantinib

Vandetanib and cabozantinib (Cabozantinib) are two representative targeted drugs currently used to treat ** medullary thyroid cancer (MTC; thyroid cancer) **. They have a close therapeutic relationship and also reflect the evolution of the concept of tumor-targeted drugs from "multi-target inhibition" to "precision targeting". Both are tyrosine kinase inhibitors (TKIs), which mainly block tumor progression by inhibiting cancer cell growth signaling pathways. However, there are obvious differences and complementarities in terms of mechanism of action, clinical positioning, drug metabolism, and drug resistance mechanisms.

Vandertanib is a first-generation multi-target TKI developed by AstraZeneca (AstraZeneca). It was approved by the US FDA for advanced medullary thyroid cancer in 2011. It is the first targeted drug for MTC. It can simultaneously inhibit multiple signaling pathways such as RET (rearrangement activated transcriptase), VEGFR (vascular endothelial growth factor receptor) and EGFR (epidermal growth factor receptor)**. Through this multi-pathway blockade, vandetanib not only inhibits the proliferation signals of tumor cells themselves, but also reduces tumor angiogenesis, thereby limiting the nutrient supply to cancer cells. The emergence of this drug provides a breakthrough treatment option for MTC patients, especially for patients carrying RET mutations, which shows a good disease control rate.

Cabozantinib (Cabozantinib) is a "second-generation multi-target TKI" that emerged after vandetanib. It was developed by Exelixis and was approved by the FDA in 2012 for the treatment of advanced MTC. It has a wider range of targets. In addition to inhibiting RET and VEGFR, it can also act on molecules such as MET (mesenchymal growth factor receptor) and AXL. These signaling pathways are closely related to tumor invasion, metastasis and drug resistance. By simultaneously inhibiting these key pathways, cabozantinib not only inhibits tumor growth, but also overcomes the possible resistance problem of vandetanib to a certain extent, allowing it to show better efficacy in patients after disease progression.

From the perspective of pharmacological effects, vandetanib is characterized by "multi-target balanced inhibition". It has a wide range of targets but relatively weak specificity. Some patients may be restricted from long-term use due to side effects or drug resistance. Cabozantinib's "precise multi-target" design is more targeted, especially in MTC patients with abnormal activation of the MET pathway, and can bring more lasting disease control. Therefore, in clinical practice, the two are often viewed as complementary treatment options. Some guidelines suggest that cabozantinib may be considered as a follow-up treatment when patients develop resistance or intolerance to vandetanib.

In addition, in terms of safety, vandetanib may cause adverse reactions such as rash, diarrhea, and abnormal heart rhythm due to its inhibition ofEGFR, while common side effects of cabozantinib include hand-foot syndrome, decreased appetite, and hypertension. Although both drugs are oral preparations, in terms of medication management, doctors usually make choices based on individual factors such as patient mutation type, tolerance, and comorbidities.

In recent years, with the emergence of RET selective inhibitors (such as Selpercatinib and Pralsetinib), the status of vandetanib and cabozantinib in the treatment of MTC has gradually changed from "first choice" to "alternative". However, they still play a key role in some patients who do not have RET mutations or are insensitive to new drugs.

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