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Druggable targets of squamous cell lung cancer.

ABSTRACT: Knowledge of molecular pathogenesis of non-small cell lung cancer has increased remarkably and changed the principles of treatment, especially during the past decade. These advancements have been limited mainly to adenocarcinoma of the lung. Recently, genetic alterations in squamous cell lung cancer (SQCLC) have been detailed and positive results of clinical trials using agents targeting these changes have indicated the potential for improved treatment outcomes for SQCLC.

SUBMITTER: Kim CH

PROVIDER: S-EPMC3884109 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Druggable targets of squamous cell lung cancer.

Kim Cheol Hyeon CH

Tuberculosis and respiratory diseases 20131224 6

Knowledge of molecular pathogenesis of non-small cell lung cancer has increased remarkably and changed the principles of treatment, especially during the past decade. These advancements have been limited mainly to adenocarcinoma of the lung. Recently, genetic alterations in squamous cell lung cancer (SQCLC) have been detailed and positive results of clinical trials using agents targeting these changes have indicated the potential for improved treatment outcomes for SQCLC. ...[more]

PMID: 24416052

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.MethodsWe investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.ResultsPD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).ConclusionsPIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.

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Druggable targets of squamous cell lung cancer.

Publications

Druggable targets of squamous cell lung cancer.

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