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Published on: July 25, 2020
Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase
Yuki Okawa1,2, Nobutaka Ebata1,2, Nayoung K D Kim3,4
1Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Introduction:
Treatment options for biliary tract cancer (BTC) are very limited. It is necessary to investigate actionable genes and candidate drugs using a sophisticated knowledgebase (KB) and characterize BTCs immunologically for evaluating the actionability of molecular and immune therapies.
Materials And Methods:
The genomic and transcriptome data of 219 patients with BTC who underwent surgery were analyzed. Actionable mutations and candidate drugs were annotated using the largest available KB of the Asian population (CancerSCAN®). Predictive biomarkers of immune checkpoint inhibitors were analyzed using DNA and RNA sequencing data.
Results:
Twenty-two actionable genes and 43 candidate drugs were annotated in 74 patients (33.8%). The most frequent actionable genes were PTEN (7.3%), CDKN2A (6.8%), KRAS (6.4%). BRCA2, CDKN2A, and FGFR2 mutations were most frequently identified in case of intrahepatic cholangiocarcinoma. PTEN and CDKN2A mutations were associated with significantly shorter overall survival. PD-L1 and PD-1 expression was significantly higher in case of extrahepatic cholangiocarcinoma and T-cell-high expression. In total, 49.7% of cases were evaluated as having actionability for molecular therapy or immune checkpoint inhibitors.
Conclusions:
Identifying actionable genes and candidate drugs using the KB contribute to the development of therapeutic drugs and personalized treatment for BTC.
Insights
This study identified actionable genes and drugs in biliary tract cancer (BTC) patients, finding that 49.7% had potential for targeted or immune therapies, paving the way for personalized BTC treatment.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Biliary tract cancer (BTC) has limited treatment options.
- Investigating actionable genes and candidate drugs is crucial for personalized therapy.
- Characterizing BTC immunologically aids in evaluating molecular and immune treatments.
Purpose of the Study:
- To identify actionable genes and candidate drugs in BTC using a comprehensive knowledgebase (KB).
- To analyze predictive biomarkers for immune checkpoint inhibitors in BTC.
- To evaluate the actionability of molecular and immune therapies for BTC patients.
Main Methods:
- Genomic and transcriptome data from 219 BTC patients were analyzed.
- Actionable mutations and drugs were annotated using the CancerSCAN® KB.
- Predictive biomarkers for immune checkpoint inhibitors were assessed via DNA and RNA sequencing.
Main Results:
- 22 actionable genes and 43 candidate drugs were identified in 33.8% of patients.
- PTEN, CDKN2A, and KRAS were the most frequent actionable genes.
- 49.7% of BTC cases showed potential for molecular or immune checkpoint inhibitor therapy.
Conclusions:
- Utilizing a KB to identify actionable genes and drugs advances therapeutic development for BTC.
- This approach supports the creation of personalized treatment strategies for biliary tract cancer.
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