Prognosis of ALK-rearranged non-small-cell lung cancer patients carrying TP53 mutations
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Updated: Sep 6, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Matteo Canale1, Elisabetta Petracci2, Paola Cravero3
1Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Abstract:
Non-small-cell lung cancer (NSCLC) is the primary cause of cancer-related death. Gene rearrangements involving the anaplastic lymphoma kinase (ALK) tyrosine kinase identify a clinical and molecular subset of NSCLC patients, who benefit from the monotherapy with ALK tyrosine kinase inhibitors. Nonetheless, responsiveness to TKIs and prognosis of these patients are influenced by several factors, including resistance mechanisms and mutations affecting genes involved in key molecular pathways of cancer cells. In a cohort of 98 NSCLC patients with ALK gene rearrangements, we investigated the role of Tumor Protein (TP53) gene mutations in predicting patients prognosis. TP53 mutations were evaluated in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).Results: In patients with available clinical and TP53 mutation information, we found that 13 patients (20.3%) were affected by TP53 mutations. Considered together, even though showing a trend, TP53 mutations were not associated with PFS and OS. Considering the different TP53 mutations by functionality in terms of disruptive and non-disruptive mutations, we observed that TP53 non-disruptive mutations were able to predict worse OS in the overall case series. Moreover, a worse PFS was seen in the subgroup of patients with TP53 non-disruptive mutation, in first-, second-, and third line of treatment. Our results show that mutations affecting TP53 gene, especially non-disruptive mutations, are able to affect prognosis of ALK-rearranged NSCLC patients.
Insights
Tumor Protein (TP53) gene mutations, particularly non-disruptive ones, impact prognosis in non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangements, affecting survival outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality.
- Anaplastic lymphoma kinase (ALK) rearrangements define a subset of NSCLC patients responsive to ALK tyrosine kinase inhibitors (TKIs).
- Prognosis in ALK-rearranged NSCLC is influenced by resistance mechanisms and mutations in key cancer pathways, including TP53.
Purpose of the Study:
- To investigate the prognostic role of Tumor Protein (TP53) gene mutations in 98 NSCLC patients with ALK gene rearrangements.
- To evaluate the association between TP53 mutations and clinical outcomes such as disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Retrospective analysis of clinical and genetic data from 98 NSCLC patients with ALK rearrangements.
- TP53 mutation status and functionality (disruptive vs. non-disruptive) were assessed.
- Correlation of TP53 mutations with DCR, ORR, PFS, and OS.
Main Results:
- TP53 mutations were identified in 20.3% of the analyzed patients.
- Overall TP53 mutations did not show a statistically significant association with PFS or OS.
- TP53 non-disruptive mutations were associated with worse overall survival (OS) and progression-free survival (PFS) across different lines of treatment.
Conclusions:
- TP53 gene mutations, especially non-disruptive types, significantly affect the prognosis of ALK-rearranged NSCLC patients.
- Non-disruptive TP53 mutations may serve as a predictive biomarker for poorer outcomes in this specific NSCLC subset.
- Further research is warranted to elucidate the mechanisms underlying TP53's influence on TKI response and survival in ALK-rearranged NSCLC.
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