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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy
Motonobu Saito1,2,3, Hiroyuki Suzuki4, Koji Kono5
1Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 1040045, Japan. mosaitoh@ncc.go.jp.
Abstract:
Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC. Interestingly, the frequency of driver gene aberrations differs according to ethnicity, sex, and smoking, which leads to differences in treatment efficacy. To date, several molecular-targeted drugs against driver genes have been developed, and several clinical trials have been conducted to evaluate the efficacy. However, targeted therapies against driver-gene-negative cases have not yet been well developed. Efforts to identify a new druggable target for such cases are currently underway. Furthermore, immune checkpoint blockade therapy might be effective for driver-negative cases, especially those with accumulated mutations.
Insights
Lung adenocarcinoma (LADC) treatment advances with targeted therapies for driver gene aberrations like EGFR mutations and ALK fusions. Research continues to find new targets for LADC cases lacking these common mutations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Lung adenocarcinoma (LADC) is a significant cause of cancer mortality.
- Targeted therapies against specific genetic aberrations have revolutionized LADC treatment.
- Identifying new therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To review current targeted therapies for LADC based on driver gene aberrations.
- To highlight the need for novel therapeutic strategies for LADC cases lacking common driver mutations.
- To explore potential new targets and immunotherapies for driver-negative LADC.
Main Methods:
- Literature review of targeted therapies and genetic aberrations in LADC.
- Analysis of clinical trial data for efficacy and toxicity of LADC treatments.
- Exploration of emerging research on novel druggable targets and immunotherapies for LADC.
Main Results:
- EGFR mutations and ALK fusions are common LADC aberrations with effective targeted therapies.
- KRAS, HER2, BRAF mutations, and RET/ROS1 fusions are other identified LADC driver aberrations.
- Treatment efficacy varies by ethnicity, sex, and smoking status, necessitating personalized approaches.
Conclusions:
- Targeted therapies have significantly improved LADC outcomes but are ineffective for driver-negative cases.
- Ongoing research focuses on identifying new druggable targets for LADC.
- Immune checkpoint blockade therapy shows promise for driver-negative LADC, particularly those with high mutation burdens.
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