Comparative analysis of therapeutic target protein expression in de novo and transformed small cell lung carcinomas using paired biopsy samples.

INTRODUCTION

Antibody-drug conjugates (ADCs) and bispecific antibodies (BiAbs) are emerging treatments for small cell lung cancer (SCLC). However, optimal patient selection remains unclear. Delta-like ligand 3 (DLL3) is a promising therapeutic target, but its clinical utility is not fully established, and data on other targetable proteins such as trophoblast cell-surface antigen 2 (TROP2) and B7-H3 remain limited. To our knowledge, no prior study has assessed multiple therapeutic targets within the same patient before and after treatment. This study examined changes in DLL3 and other targets in de novo and transformed SCLC.

MATERIALS AND

METHODS

We retrospectively analyzed 15 patients with SCLC (9 de novo and 6 transformed SCLC) with tumor biopsies at diagnosis and progression. Immunohistochemistry assessed DLL3, TROP2, B7-H3, MET, and HER2. H-score changes, with a ≥ 100-point difference considered significant.

RESULTS

In de novo SCLC, DLL3 fluctuated in 3/9 cases, B7-H3 and MET increased in 2/9 and 1/9 cases, respectively, while HER2 became negative in 1/9 case. Protein co-expression was seen in 5 of 9 cases. In transformed SCLC, DLL3 expression increased in 6/6 cases, while TROP2 and HER2 were downregulated. B7-H3 and MET showed a decreasing trend in 4/5 cases. Co-expression was observed in 3/5 cases, all showing DLL3 and B7-H3 positivity, with additional co-expression of MDM2 or MET.

CONCLUSION

Therapeutic target proteins in SCLC exhibit dynamic changes, emphasizing the need for biomarker-driven strategies. Rebiopsy may guide therapeutic decisions, and further research is needed to optimize patient selection for ADCs and BiAbs.