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Published on: April 6, 2016
In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer
Ryohei Miyazaki1, Takashi Anayama1, Kentaro Hirohashi1
1Division of Thoracic Surgery, Department of Surgery II, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
Background:
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI) test and collagen gel droplet embedded culture drug sensitivity test (CD-DST) are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.
Methods:
The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.
Results:
HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003). The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026) in CD-DST.
Conclusions:
In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.
Insights
In vitro drug sensitivity tests, succinate dehydrogenase inhibition (SDI) and collagen gel droplet embedded culture drug sensitivity test (CD-DST), can predict patient response to lung cancer molecular targeted drugs based on EGFR gene status.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Targeted therapies like EGFR-TKIs and ALK inhibitors have transformed lung cancer treatment.
- Pre-treatment screening for EGFR mutations or EML4-ALK fusions is crucial for predicting treatment response.
- In vitro drug sensitivity tests, including SDI and CD-DST, offer potential for predicting patient responses to cytotoxic drugs.
Purpose of the Study:
- To evaluate the utility of in vitro drug sensitivity tests (SDI and CD-DST) in predicting clinical responses to molecular targeted drugs in lung cancer.
- To correlate the results of SDI and CD-DST with EGFR mutation status in lung cancer patients.
Main Methods:
- Confirmed growth inhibitory effects of erlotinib and crizotinib on lung cancer cell lines using SDI and CD-DST.
- Assessed the sensitivity of 35 surgically resected lung cancer cases to erlotinib using SDI or CD-DST.
- Compared in vitro drug sensitivity results with EGFR mutation status.
Main Results:
- Lung cancer cell lines with specific EGFR mutations (HCC827) or ALK fusions (H3122) showed higher sensitivity to erlotinib and crizotinib, respectively.
- SDI test showed significantly lower cell viability in EGFR-mutant lung cancer (60.0%) compared to wild-type (86.8%).
- CD-DST also demonstrated significantly lower cell viability in EGFR-mutant lung cancer (33.5%) compared to wild-type (79.0%).
Conclusions:
- In vitro drug sensitivity testing using SDI or CD-DST correlates with EGFR gene status in lung cancer.
- SDI and CD-DST are potentially valuable tools for predicting patient response to molecular targeted therapies in lung cancer.
