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Co-occurring KEAP1 and TP53 mutations in lung squamous cell carcinoma induced primary resistance to thoracic
Rumi Nishimura1, Tatsuya Yoshida1, Masahiro Torasawa1
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Abstract:
In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1-NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62-year-old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first-line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma.
Insights
KEAP1 and TP53 mutations in lung squamous cell carcinoma patients may predict resistance to radiotherapy. This case highlights the need for genetic stratification in treatment strategies for improved outcomes.
Area of Science:
- Oncology
- Genetics
- Radiotherapy
Background:
- KEAP1 and TP53 mutations frequently co-occur in lung squamous cell carcinoma.
- Preclinical data suggest KEAP1-NRF2 pathway activation confers radioresistance.
Observation:
- A patient with advanced lung squamous cell carcinoma harboring both KEAP1 and TP53 mutations exhibited primary resistance to thoracic radiotherapy.
- Despite first-line pembrolizumab and chemotherapy, the patient experienced disease progression and subsequent radiation therapy failure.
Findings:
- The co-occurrence of KEAP1 and TP53 mutations was associated with clinical radioresistance in this lung squamous cell carcinoma case.
- Tumor progression was observed within the radiation field, indicating treatment ineffectiveness.
Implications:
- Genetic stratification, including KEAP1 and TP53 mutation status, is crucial for tailoring lung squamous cell carcinoma treatment strategies.
- Personalized radiotherapy approaches may improve outcomes for patients with specific mutation profiles.
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