TP53 Alterations Are Associated With Poor Response to Lenvatinib in Patients With Advanced Thyroid Cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Limited data exist on the association between TP53 mutations and multikinase inhibitor (MKI) response in thyroid cancer (TC).
• Understanding predictive biomarkers for MKI therapy is crucial for optimizing patient outcomes in advanced TC.

Purpose of the Study:

• To investigate the impact of TP53 mutations on lenvatinib (LEN) response in advanced TC.
• To evaluate TP53 status as a predictive biomarker for lenvatinib treatment efficacy in vitro and in patient cohorts.

Main Methods:

• Analysis of TP53 mutations and p53 protein expression in 30 advanced TC tumor tissues from patients treated with lenvatinib.
• Correlation of molecular profiles with clinical-pathological features and lenvatinib response.
• In vitro evaluation of lenvatinib sensitivity in TP53-defective and TP53-proficient TC cell lines.

Main Results:

• TP53 mutations significantly correlated with a poor response to lenvatinib (p=0.005).
• Patients with TP53 mutations exhibited significantly shorter progression-free survival (PFS) and overall survival (OS) (p<0.0001 and p=0.0007, respectively).
• Altered nuclear p53 protein expression also predicted shorter PFS and OS, consistent with findings in TP53-mutated cell lines.

Conclusions:

• TP53 alterations are a significant predictor of poor response to lenvatinib in advanced TC.
• Evaluation of TP53 mutations and p53 expression may aid in patient stratification before initiating MKI therapy.
• This study provides novel insights into the role of TP53 in lenvatinib resistance in thyroid cancer.