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Updated: Jun 13, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Comprehensive landscape of gastric cancer-targeted therapy and identification of CSNK2A1 as a potential target
Liang Zhang1,2, Jiaqi Yang1, Yingpeng Huang1
1Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China.
Objective:
To conduct a comprehensive analysis of the landscape of gastric cancer (GC)-targeted therapy clinical trials and identify potential therapeutic targets.
Methods:
A systematic search and analysis of the Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve all GC clinical trials published up to June 30, 2022. Approved therapeutic targets for 11 common cancers were compiled and analyzed. The role of CSNK2A1 in GC was investigated using bioinformatics tools such as GEPIA, KMPLOT, SangerBox, STRING, ACLBI, and TIMER. Four gastric cancer cell lines (AGS, HGC, MGC, BGC) and one normal gastric mucosa cell line (GES-1) were utilized to assess the sensitivity to the CSNK2A1 inhibitor CX-4945. Quantitative real-time polymerase chain reaction (qPCR) was employed to quantify the cellular expression of CSNK2A1. Cellular apoptosis was evaluated using flow cytometry and Western blot analysis.
Results:
The failure rate of GC randomized controlled clinical trials (RCTs) was strikingly high, accounting for 74.29 % (26/35) of the trials. Among the 35 approved targets in 11 different cancers, 13 targets were rigorously evaluated and identified as potential therapeutic targets for GC. Bioinformatics analysis revealed that CSNK2A1 is closely associated with multiple biological characteristics in GC, and its increased expression correlated significantly with enhanced sensitivity to CX-4945 treatment. Flow cytometry and Western blot analysis consistently demonstrated concentration-dependent apoptosis induced by CX-4945 in GC cell lines.
Conclusions:
The high failure rate of GC clinical trials highlights the need for a more scientific and precise approach in target identification and clinical trial design. CSNK2A1 emerges as a promising therapeutic target for GC, and its expression level could potentially serve as a biomarker for predicting sensitivity to CX-4945 treatment. Further research is warranted to elucidate the underlying molecular mechanisms and validate the clinical significance of CSNK2A1 in GC therapy.
Insights
Gastric cancer (GC) targeted therapy trials have a high failure rate. CSNK2A1 is a promising target, with its expression predicting sensitivity to CX-4945 treatment in GC.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trial Analysis
Background:
- Gastric cancer (GC) targeted therapy clinical trials exhibit a high failure rate, necessitating improved target identification strategies.
- Existing approved therapeutic targets for common cancers were analyzed for their potential application in GC.
Purpose of the Study:
- To comprehensively analyze the landscape of gastric cancer (GC)-targeted therapy clinical trials.
- To identify novel and effective therapeutic targets for GC.
- To investigate the role of CSNK2A1 as a potential therapeutic target in GC.
Main Methods:
- Systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL) for GC clinical trials up to June 2022.
- Bioinformatic analysis using GEPIA, KMPLOT, SangerBox, STRING, ACLBI, and TIMER to investigate CSNK2A1 in GC.
- In vitro sensitivity assessment of GC cell lines to the CSNK2A1 inhibitor CX-4945.
- Quantitative real-time polymerase chain reaction (qPCR), flow cytometry, and Western blot analysis to evaluate CSNK2A1 expression and apoptosis.
Main Results:
- A high failure rate (74.29%) was observed in GC randomized controlled clinical trials (RCTs).
- Thirteen of 35 approved targets across 11 cancers were identified as potential GC therapeutic targets.
- CSNK2A1 expression was significantly correlated with GC biological characteristics and enhanced sensitivity to CX-4945.
- CX-4945 treatment induced concentration-dependent apoptosis in GC cell lines.
Conclusions:
- The high failure rate in GC clinical trials underscores the need for precise target identification and optimized trial design.
- CSNK2A1 presents a promising therapeutic target for GC, with its expression potentially serving as a predictive biomarker for CX-4945 treatment response.
- Further research is essential to validate the clinical significance and underlying mechanisms of CSNK2A1 in GC therapy.
