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Updated: Mar 12, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors:
Yuko Tanabe1,2,3, Hitoshi Ichikawa4,5, Takashi Kohno4
1Department of Experimental Therapeutics, Exploratory Oncology Research & Clinical Center, National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Abstract:
It is still controversial whether comprehensive genome screening of target molecules by next generation sequencing (NGS) is needed to increase clinical efficacy of investigational drugs or accelerate drug development, although several studies are being carried out. Therefore, we performed a prospective study to evaluate the feasibility of comprehensive gene screening in this setting. Our findings indicate that actionable alterations were identified in 45% of the analyzed patients, most frequently in those with breast cancer. Common actionable alterations were found in PIK3CA mutation, BRCA2 mutation, ERBB2 amplification, and CCND1 amplification. In total, 22% of the analyzed patients could be entered into phase I clinical trials, and 8% of them were treated with "matched" drugs. Among patients who received matched therapies, response and disease control rates were 33 and 78%, respectively. On the other hand, in the patients who received "non-matched" therapy, the objective response rate was 6%. We believe this data indicates that NGS-based molecular pre-screening is a potent platform for use before patient entry into phase I trials.
Insights
Comprehensive genome screening using next-generation sequencing (NGS) identified actionable alterations in 45% of patients, guiding targeted therapy. This molecular pre-screening enhances clinical trial eligibility and treatment matching for investigational drugs.
Area of Science:
- Oncology
- Genomics
- Clinical Pharmacology
Background:
- The clinical utility of comprehensive genome screening via next-generation sequencing (NGS) for investigational drugs remains debated.
- Prospective studies are needed to assess the feasibility and impact of NGS-based molecular pre-screening in drug development.
- Identifying actionable genomic alterations can potentially improve clinical efficacy and accelerate drug development pipelines.
Discussion:
- Actionable genomic alterations were identified in 45% of patients, predominantly in breast cancer cases.
- Frequent alterations included PIK3CA mutations, BRCA2 mutations, ERBB2 amplification, and CCND1 amplification.
- NGS facilitated entry into phase I clinical trials for 22% of patients, with 8% receiving matched therapies.
Key Insights:
- Matched therapies based on NGS results yielded a 33% objective response rate and 78% disease control rate.
- In contrast, non-matched therapies showed a significantly lower objective response rate of 6%.
- NGS-based molecular pre-screening demonstrates potential as a valuable tool for patient stratification in early-phase clinical trials.
Outlook:
- This study supports the integration of NGS for molecular pre-screening prior to phase I trial enrollment.
- Further research should explore the long-term outcomes and cost-effectiveness of NGS-guided therapeutic strategies.
- Expanding comprehensive genomic profiling may optimize patient selection and enhance the success rates of novel cancer therapies.
