2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.06B.14 Differential Expression in Potential Therapeutic Target Protein by Treatment in Small Cell Lung Cancer with and without Transformation

EP.06B.14 Differential Expression in Potential Therapeutic Target Protein by Treatment in Small Cell Lung Cancer with and without Transformation

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This study explores the differential expression of potential therapeutic target proteins in small cell lung cancer (SCLC) cases both in de novo and transformed scenarios, particularly focusing on the impact of treatments. The research was conducted using specimens from SCLC patients collected from 2014 to 2023 at the National Cancer Center Hospital in Tokyo.<br /><br />The study specifically looked at the expressions of various proteins such as DLL3, TROP2, MET, HER2, and B7-H3. The expressions were evaluated based on H-scores, except for HER2 which followed a predefined scale. An important finding is the increased expression of DLL3 across all transformed SCLC cases, indicating its potential as a therapeutic target. Conversely, TROP2, MET, and HER2 tended to be downregulated after EGFR-TKI treatment in transformed cases, implying resistance due to transformation rather than treatment.<br /><br />In de novo SCLC, variability was observed, with a third of cases showing altered predominant subtypes. Interestingly, radiotherapy and immunotherapy were associated with increased DLL3 expression, suggesting a potential role of these treatments in modulating target protein expression.<br /><br />The results suggest that in cases of EGFR mutation positive non-small cell lung cancer transformed to SCLC, DLL3 overexpression is notable, supporting its consideration as a therapy target. TROP2, MET, and HER2 alterations are seen differently, pointing to transformation-induced resistance rather than direct drug influence. In de novo cases, further exploration is advised by biopsy when DLL3 expression variation occurs following ICI or CRT treatments. Overall, the study contributes to understanding the biology of SCLC and informing treatment pathways, emphasizing personalized strategies based on specific biomarker expression profiles.

Asset Subtitle

Saori Murata

Meta Tag

Speaker Saori Murata

Topic Pathology and Biomarkers

Keywords

small cell lung cancer

therapeutic targets

protein expression

DLL3

TROP2

MET

HER2

B7-H3

EGFR-TKI resistance

biomarker profiles