ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2014
A high content clonogenic survival drug screen identifies mek inhibitors as potent radiation sensitizers for KRAS mutant non-small-cell lung cancer.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
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- Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.Cancer science · 2026Article
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- The Effect of AZD5153 on Radiosensitivity in Pancreatic Cancer Cells Through ATM-chk1 Pathway.Drug design, development and therapy · 2026Article
- Impacts of co-mutations in oligometastatic and oligoprogressive non-small cell lung cancer withTranslational lung cancer research · 2025Review
- A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas.Frontiers in immunology · 2025Article
- Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?Scientific reports · 2024Article
- High-Content and High-Throughput Clonogenic Survival Assay Using Fluorescence Barcoding.Cancers · 2023Article
- A High Throughput Screen with a Clonogenic Endpoint to Identify Radiation Modulators of Cancer.Radiation research · 2023Article
- Recent progress of hydrogel-based local drug delivery systems for postoperative radiotherapy.Frontiers in oncology · 2023Review
- Radio-sensitizing effect of MEK inhibition in glioblastoma in vitro and in vivo.Journal of cancer research and clinical oncology · 2023Article
- Translation of Precision Medicine Research Into Biomarker-Informed Care in Radiation Oncology.Seminars in radiation oncology · 2022Review
- Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer.Cancer treatment and research communications · 2022Article
- High-Content Clonogenic Survival Screen to Identify Chemoradiation Sensitizers.International journal of radiation oncology, biology, physics · 2021Article
- Screening and Validation of Molecular Targeted Radiosensitizers.International journal of radiation oncology, biology, physics · 2021Article
- National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer.Cancer · 2019Review
- Enhanced dependency of KRAS-mutant colorectal cancer cells on RAD51-dependent homologous recombination repair identified from genetic interactions in Saccharomyces cerevisiae.Molecular oncology · 2017Article
- Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations.Translational oncology · 2016Review
- A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment.BMC cancer · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
introductionTraditional clonogenic survival and high throughput colorimetric assays are inadequate as drug screens to identify novel radiation sensitizers. We developed a method that we call the high content clonogenic survival assay (HCSA) that will allow screening of drug libraries to identify candidate radiation sensitizers.
methodsDrug screen using HCSA was done in 96 well plates. After drug treatment, irradiation, and incubation, colonies were stained with crystal violet and imaged on the INCell 6000 (GE Health). Colonies achieving 50 or more cells were enumerated using the INCell Developer image analysis software. A proof-of-principle screen was done on the KRAS mutant lung cancer cell line H460 and a Custom Clinical Collection (146 compounds).
resultsMultiple drugs of the same class were found to be radiation sensitizers and levels of potency seemed to reflect the clinical relevance of these drugs. For instance, several PARP inhibitors were identified as good radiation sensitizers in the HCSA screen. However, there were also a few PARP inhibitors not found to be sensitizing that have either not made it into clinical development, or in the case of BSI-201, was proven to not even be a PARP inhibitor. We discovered that inhibitors of pathways downstream of activated mutant KRAS (PI3K, AKT, mTOR, and MEK1/2) sensitized H460 cells to radiation. Furthermore, the potent MEK1/2 inhibitor tramenitib selectively enhanced radiation effects in KRAS mutant but not wild-type lung cancer cells.
conclusionsDrug screening for novel radiation sensitizers is feasible using the HCSA approach. This is an enabling technology that will help accelerate the discovery of novel radiosensitizers for clinical testing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.