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

Valentina Cirello1,2, Carla Colombo1,2, Delfina Tosi3

  • 1Department of Endocrine and Metabolic Diseases, Endocrine Oncology Unit, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy.

The Journal of Clinical Endocrinology and Metabolism
|February 1, 2025
PubMed
Abstract

Insights

TP53 mutations predict a poor response to lenvatinib in advanced thyroid cancer. Patients with TP53 alterations experienced shorter progression-free and overall survival, highlighting a potential biomarker for treatment selection.

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.
Keywords:
TP53advanced thyroid cancerlenvatinibmultikinase inhibitorspoorly differentiated thyroid cancerresistance to MKI

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