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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Gene aberrations for precision medicine against lung adenocarcinoma
Motonobu Saito1,2, Kouya Shiraishi1, Hideo Kunitoh3
1Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
Lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, is often triggered by an aberration in a driver oncogene in tumor cells. Examples of such aberrations are EGFR mutation and ALK fusion. Lung adenocarcinoma harboring such mutations can be treated with anticancer drugs that target the aberrant gene products. Additional oncogene aberrations, including RET, ROS1, and NRG1 fusions, skipping of exon 14 of MET, and mutations in BRAF, HER2, NF1, and MEK1, were recently added to the list of such "druggable" driver oncogene aberrations, and their responses to targeted therapies are currently being evaluated in clinical trials. However, approximately 30% and 50% of LADCs in patients in Japan and Europe/USA, respectively, lack the driver oncogene aberrations listed above. Therefore, novel therapeutic strategies, such as those that exploit the vulnerabilities of cancer cells with non-oncogene aberrations, are urgently required. This review summarizes the current status of research on precision medicine against LADC and enumerates the research priorities for the near future.
Insights
Lung adenocarcinoma (LADC) treatments target specific gene mutations. New research explores therapies for LADCs lacking these common driver oncogene aberrations, addressing a significant unmet need.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Lung adenocarcinoma (LADC) is the most common lung cancer subtype.
- Many LADCs are driven by specific oncogene aberrations like EGFR mutations and ALK fusions.
- Targeted therapies exist for LADCs with known "druggable" driver oncogene aberrations.
Purpose of the Study:
- To review the current landscape of precision medicine for lung adenocarcinoma.
- To identify and prioritize future research directions for LADC treatment.
- To address the need for novel therapeutic strategies in LADCs lacking common driver aberrations.
Main Methods:
- Literature review of current research on lung adenocarcinoma precision medicine.
- Analysis of identified "druggable" driver oncogene aberrations and targeted therapies.
- Enumeration of research priorities for future LADC therapeutic development.
Main Results:
- Several oncogene aberrations (RET, ROS1, MET, BRAF, HER2, NF1, MEK1) are now recognized as targets for LADC therapy.
- A significant proportion of LADCs (30% in Japan, 50% in Europe/USA) lack these common driver oncogene aberrations.
- Clinical trials are evaluating the efficacy of targeted therapies for these newly identified aberrations.
Conclusions:
- Precision medicine has advanced LADC treatment by targeting specific driver oncogene aberrations.
- A substantial subset of LADCs remains untargeted by current precision therapies, necessitating novel approaches.
- Future research should focus on exploiting vulnerabilities in LADC cells with non-oncogene aberrations.
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