Related Experiment Video
Updated: Apr 23, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Comparative analysis of therapeutic target protein expression in de novo and transformed small cell lung carcinomas
Saori Murata1, Jumpei Kashima2, Hidehito Horinouchi3
1Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Minato-ku, Tokyo, Japan.
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.
Insights
Therapeutic targets like DLL3 in small cell lung cancer (SCLC) change during treatment. Rebiopsy can guide decisions for antibody-drug conjugates (ADCs) and bispecific antibodies (BiAbs) in SCLC patients.
Area of Science:
- Oncology
- Translational Research
Background:
- Emerging treatments for small cell lung cancer (SCLC) include antibody-drug conjugates (ADCs) and bispecific antibodies (BiAbs).
- Optimal patient selection for these therapies is unclear, with limited data on key targets like Delta-like ligand 3 (DLL3), trophoblast cell-surface antigen 2 (TROP2), and B7-H3.
- This study is the first to assess multiple therapeutic targets in SCLC patients before and after treatment.
Purpose of the Study:
- To investigate the dynamic changes of therapeutic target proteins in de novo and transformed SCLC.
- To evaluate the clinical utility of assessing multiple targets, including DLL3, TROP2, B7-H3, MET, and HER2, over the course of SCLC treatment.
- To inform biomarker-driven strategies for patient selection in SCLC therapy.
Main Methods:
- Retrospective analysis of tumor biopsies from 15 SCLC patients (9 de novo, 6 transformed) at diagnosis and progression.
- Immunohistochemistry was used to assess the expression levels of DLL3, TROP2, B7-H3, MET, and HER2.
- Significant changes in H-score were defined as a difference of ≥100 points.
Main Results:
- In de novo SCLC, DLL3 expression fluctuated in 3/9 cases, while B7-H3 and MET increased in 2/9 and 1/9 cases, respectively. HER2 expression became negative in 1/9 case.
- Transformed SCLC showed increased DLL3 expression in all 6 cases, with downregulation of TROP2 and HER2. B7-H3 and MET generally decreased.
- Protein co-expression patterns varied, with DLL3 and B7-H3 frequently co-expressed in transformed SCLC.
Conclusions:
- Therapeutic target protein expression in SCLC is dynamic and changes throughout treatment.
- Biomarker-driven strategies are essential for optimizing patient selection for ADCs and BiAbs.
- Rebiopsy may be a valuable tool to guide therapeutic decisions in SCLC management.
