Hypothyroidism Side Effect in Patients Treated with Sunitinib or Sorafenib: Clinical and Structural Analyses

Area of Science:

• Oncology
• Pharmacology
• Toxicology

Background:

• Tyrosine kinase inhibitors (TKIs) are effective cancer treatments but can cause adverse effects like hypothyroidism.
• The mechanisms behind TKI-induced hypothyroidism and varying drug risks (e.g., sunitinib vs. sorafenib) are not fully understood.

Purpose of the Study:

• To investigate the pharmacological differences between sunitinib and sorafenib concerning hypothyroidism.
• To identify potential molecular mechanisms underlying sunitinib-induced thyroid dysfunction.

Main Methods:

• Analysis of clinical data from the FDA Adverse Event Reporting System (FAERS).
• In silico drug-protein interaction analysis using molecular docking.

Main Results:

• Sunitinib was statistically associated with a higher incidence of hypothyroidism compared to sorafenib in FAERS data.
• Three proteins (retinoid X receptor alpha, retinoic acid receptors beta and gamma) were identified as specific binding targets for sunitinib, but not sorafenib.
• These identified proteins are known to interact with thyroid hormone receptors, suggesting a mechanism for sunitinib's effect on thyroid function.

Conclusions:

• Sunitinib poses a greater risk for hypothyroidism than sorafenib, potentially due to interactions with specific retinoid receptors.
• An integrated approach combining clinical data and in silico drug-target analysis can elucidate the molecular basis of adverse drug reactions.