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Updated: Aug 2, 2026
Establishment and Characterization of Small Bowel Neuroendocrine Tumor Spheroids
Published on: October 14, 2019
Molecular characterization of Chinese patients with small bowel adenocarcinoma
Bryan Jin1, Bin Lv1, Zhengqing Yan2
1Department of Digestive Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Purpose:
Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA.
Methods:
Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS.
Results And Conclusions:
The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.
Insights
Circulating tumor DNA (ctDNA) analysis can identify genetic alterations in small bowel adenocarcinoma (SBA). Targeting the RTK-RAS-MAPK pathway in ctDNA led to significant tumor shrinkage in a patient with advanced SBA.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer.
- Obtaining tissue samples from SBA lesions is challenging, hindering research and treatment development.
- Circulating tumor DNA (ctDNA) analysis offers a minimally invasive method for SBA investigation.
Purpose of the Study:
- To analyze the molecular characteristics of SBA using next-generation sequencing (NGS).
- To validate ctDNA as a reliable tool for profiling SBA mutations.
- To explore targeted therapy based on ctDNA findings in an advanced SBA case.
Main Methods:
- NGS analysis of 336 tissue and plasma samples from SBA patients (January 2017 - August 2021).
- Comparison of mutation profiles between tumor tissue and ctDNA.
- Application of ctDNA analysis for treatment selection in a chemotherapy-resistant patient.
Main Results:
- Commonly altered genes in SBA tissues include TP53, KRAS, and APC.
- The RTK-RAS-MAPK pathway is frequently affected and shows potential as a therapeutic target.
- ctDNA mutation profiling mirrored tissue sample findings.
- A patient treated with MEK + EGFR inhibitors based on ctDNA alterations achieved 76.33% tumor shrinkage.
Conclusions:
- ctDNA analysis is a viable method for characterizing SBA molecular alterations.
- The RTK-RAS-MAPK pathway is a promising target for SBA treatment.
- This study provides insights into SBA molecular landscape and supports ctDNA-guided therapy.
