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Updated: Dec 23, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Targeted deep sequencing contributes to guiding personalized targeted therapy for advanced biliary tract cancer
Feiling Feng1, Qingbao Cheng1, Dadong Zhang2
1Department of Biliary I, Shanghai Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai 200438, P.R. China.
Abstract:
Targeted therapy based on specific genetic alterations has been proven to be an effective treatment for various types of cancer. In the present study, we aimed to explore the efficacy of personalized targeted therapy guided by targeted deep sequencing for patients with advanced biliary tract cancer (BTC) after non‑radical resection. Targeted deep sequencing was performed on 49 patients with BTC, to whom biologic agents were recommended. Among 32 patients with stage IV and R2 resection (a non‑radical resection), 21 patients underwent conventional chemotherapy (mGEMOX), while the remaining 11 patients received a personalized targeted agent. The genomic landscape of the 49 patients with BTC was determined and the results showed that genetic alterations were enriched in the ERBB family and cell cycle pathway. After a median follow‑up of 12 months, the 11 BTC patients with personalized targeted therapy showed a median progression‑free survival (PFS) of 4.5 months (2.5‑20.5 months), a median overall survival (OS) of 12.9 months (4.7‑24.8 months) and a disease control rate (DCR) of 63.6%. In the other 21 BTC patients, who were undergoing conventional chemotherapy, the BTC patients had a median PFS of 1.5 months (0.5‑11.6 months), a median OS of 4.1 months (1.3‑18.4 months), and a DCR of 33.3%. In addition, 36.4% of the patients in the personalized targeted therapy group experienced grade >2 treatment‑related toxicity vs. 19.0% of patients in the conventional chemotherapy group. This real‑world study suggests that targeted deep sequencing contributes to the guidance of personalized targeted therapy based on individual actionable mutations, which may benefit advanced BTC patients undergoing non‑radical resection.
Insights
Personalized targeted therapy guided by deep sequencing improved outcomes for advanced biliary tract cancer (BTC) patients after non-radical resection. This approach showed longer progression-free survival and overall survival compared to conventional chemotherapy.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Targeted therapy offers effective cancer treatment based on genetic alterations.
- Biliary tract cancer (BTC) is a challenging disease, especially after non-radical resection.
- Identifying actionable mutations is crucial for guiding treatment decisions.
Purpose of the Study:
- To evaluate the efficacy of personalized targeted therapy guided by targeted deep sequencing in advanced BTC patients with non-radical resection.
- To compare outcomes between patients receiving targeted therapy and those undergoing conventional chemotherapy.
Main Methods:
- Targeted deep sequencing was performed on 49 advanced BTC patients.
- Biologic agents were recommended based on sequencing results.
- A cohort of 32 patients with stage IV and R2 resection were divided into two groups: 21 received conventional chemotherapy (mGEMOX) and 11 received personalized targeted agents.
Main Results:
- The genomic landscape revealed enriched alterations in the ERBB family and cell cycle pathways.
- Personalized targeted therapy group (11 patients) showed median progression-free survival (PFS) of 4.5 months and median overall survival (OS) of 12.9 months, with a disease control rate (DCR) of 63.6%.
- Conventional chemotherapy group (21 patients) had median PFS of 1.5 months, median OS of 4.1 months, and DCR of 33.3%.
- Higher grade toxicity (>2) was observed in 36.4% of the targeted therapy group versus 19.0% in the conventional chemotherapy group.
Conclusions:
- Targeted deep sequencing can guide personalized targeted therapy for advanced BTC patients.
- This approach may offer significant clinical benefits for patients undergoing non-radical resection.
- Personalized therapy demonstrated improved survival outcomes and disease control compared to standard chemotherapy.
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