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A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Predicting the outcome of chemotherapy for lung cancer
Rafael Rosell1, Fabiana Cecere, Mariacarmela Santarpia
1Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Spain, and Medical Oncology Unit, University of Messina, Italy. rrosell@ico.scs.es
Abstract:
Lung cancer is a worldwide problem. At the time of diagnosis, 50% of patients have advanced incurable disease. Different chemotherapy combinations--with or without targeted therapies--yield similar results despite the continuous efforts of clinicians. However, molecular biological studies have already shed a great deal of light on the existence of multiple genetic aberrations that can be useful for customizing treatment. mRNA transcripts involved in DNA repair pathways, such as ERCC1 and BRCA1, confer selective resistance to cisplatin or taxanes, whereas thioredoxin confers a broad spectrum of chemoresistance. Polymorphisms in DNA repair genes and methylation of checkpoint genes in circulating serum DNA could become important predictive markers of survival in certain cisplatin-based regimens. Epidermal growth factor receptor tyrosine kinase mutations are the crux of targeted therapies, whereas epithelial-mesenchymal transitions and HER3 mRNA levels are promising ancillary markers for treatment with epidermal growth factor receptor tyrosine kinase inhibitors.
Insights
Molecular markers can help personalize lung cancer treatment. DNA repair gene variations and EGFR mutations guide chemotherapy and targeted therapy selection for improved patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer presents a significant global health challenge, with half of diagnoses occurring at advanced, incurable stages.
- Current chemotherapy regimens, even with targeted therapies, offer limited efficacy, necessitating novel treatment strategies.
Purpose of the Study:
- To explore the role of molecular aberrations in customizing lung cancer treatment.
- To identify potential biomarkers for predicting patient response to chemotherapy and targeted therapies.
Main Methods:
- Analysis of mRNA transcripts involved in DNA repair pathways (e.g., ERCC1, BRCA1, thioredoxin).
- Investigation of DNA repair gene polymorphisms and checkpoint gene methylation in circulating serum DNA.
- Evaluation of epidermal growth factor receptor (EGFR) tyrosine kinase mutations, epithelial-mesenchymal transitions, and HER3 mRNA levels.
Main Results:
- ERCC1 and BRCA1 mRNA levels correlate with resistance to specific chemotherapies like cisplatin and taxanes.
- Thioredoxin mRNA indicates broad chemoresistance.
- Polymorphisms in DNA repair genes and serum DNA methylation may predict survival in cisplatin-based treatments.
- EGFR tyrosine kinase mutations are key targets for therapy, with HER3 mRNA and epithelial-mesenchymal transitions serving as ancillary markers.
Conclusions:
- Molecular profiling, including DNA repair gene status and EGFR mutations, is crucial for tailoring lung cancer treatment.
- Biomarkers like ERCC1, BRCA1, and EGFR mutations can guide the selection of effective chemotherapy and targeted therapies.
- Circulating DNA markers show promise for predicting treatment outcomes in lung cancer patients.
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