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Updated: Mar 20, 2026
MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
Published on: October 26, 2017
Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression
Eric Polley1, Mark Kunkel1, David Evans1
1Affiliations of authors: Molecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD (DE, TS, RD, JL, CO, RR, MS, JC, EH, NF, AM); Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis (MK, GK, JM, BAT), Biometric Research Program, Division of Cancer Treatment and Diagnosis (EP, DS), and Cancer Therapy Evaluation Program (SM), National Cancer Institute, Rockville, MD.
Background:
Small cell lung carcinoma (SCLC) is an aggressive, recalcitrant cancer, often metastatic at diagnosis and unresponsive to chemotherapy upon recurrence, thus it is challenging to treat.
Methods:
Sixty-three human SCLC lines and three NSCLC lines were screened for response to 103 US Food and Drug Administration-approved oncology agents and 423 investigational agents. The investigational agents library was a diverse set of small molecules that included multiple compounds targeting the same molecular entity. The compounds were screened in triplicate at nine concentrations with a 96-hour exposure time using an ATP Lite endpoint. Gene expression was assessed by exon array, and microRNA expression was derived by direct digital detection. Activity across the SCLC lines was associated with molecular characteristics using pair-wise Pearson correlations.
Results:
Results are presented for inhibitors of targets: BCL2, PARP1, mTOR, IGF1R, KSP/Eg5, PLK-1, AURK, and FGFR1. A relational map identified compounds with similar patterns of response. Unsupervised microRNA clustering resulted in three distinct SCLC subgroups. Associating drug response with micro-RNA expression indicated that lines most sensitive to etoposide and topotecan expressed high miR-200c-3p and low miR-140-5p and miR-9-5p. The BCL-2/BCL-XL inhibitors produced similar response patterns. Sensitivity to ABT-737 correlated with higher ASCL1 and BCL2. Several classes of compounds targeting nuclear proteins regulating mitosis produced a response pattern distinct from the etoposide response pattern.
Conclusions:
Agents targeting nuclear kinases appear to be effective in SCLC lines. Confirmation of SCLC line findings in xenografts is needed. The drug and compound response, gene expression, and microRNA expression data are publicly available at http://sclccelllines.cancer.gov.
Insights
This study screened 63 small cell lung cancer (SCLC) cell lines against numerous oncology drugs. Certain targeted agents showed promise, with drug response linked to specific microRNA profiles in SCLC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options.
- SCLC is often diagnosed at a metastatic stage and becomes resistant to chemotherapy upon recurrence.
- Developing effective therapies for SCLC remains a significant clinical challenge.
Purpose of the Study:
- To screen a large library of approved and investigational oncology agents against human SCLC cell lines.
- To identify potential therapeutic targets and drug candidates for SCLC treatment.
- To correlate drug response with molecular characteristics, including gene and microRNA expression.
Main Methods:
- Screened 63 SCLC and 3 NSCLC cell lines against 103 FDA-approved and 423 investigational oncology agents.
- Utilized a 96-hour drug exposure with nine concentrations and an ATP Lite endpoint for response assessment.
- Assessed gene expression via exon array and microRNA expression via direct digital detection; correlated activity with molecular profiles.
Main Results:
- Identified promising responses to inhibitors targeting BCL2, PARP1, mTOR, IGF1R, KSP/Eg5, PLK-1, AURK, and FGFR1.
- Discovered three distinct SCLC subgroups based on unsupervised microRNA clustering.
- Linked sensitivity to etoposide and topotecan with high miR-200c-3p and low miR-140-5p/miR-9-5p expression; noted similar patterns for BCL-2/BCL-XL inhibitors.
Conclusions:
- Agents targeting nuclear kinases demonstrate potential efficacy in SCLC cell lines.
- Further validation of these findings in preclinical xenograft models is warranted.
- Comprehensive drug response, gene expression, and microRNA data are publicly accessible for further research.
