ArticleInternational journal of molecular sciences2020
Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Deep learning unlocks label-free viability assessment of cancer spheroids in microfluidics.Lab on a chip · 2024Article
- Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Article
- CC-115 Mediates GSDME-Dependent Pyroptosis in Lung Adenocarcinoma Through the Akt/Bax Pathway.Journal of Cancer · 2023Article
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Newly Synthesized Melphalan Analogs Induce DNA Damage and Mitotic Catastrophe in Hematological Malignant Cancer Cells.International journal of molecular sciences · 2022Article
- Article
- Kinase inhibitors increase individual radiation sensitivity in normal cells of cancer patients.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2022Article
- An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth.Cell death discovery · 2022Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- Article
- PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation.Genes · 2021Article
- Targeting Genome Stability in Melanoma-A New Approach to an Old Field.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CC-115 is a dual inhibitor of the mechanistic target of rapamycin (mTOR) kinase and the DNA-dependent protein kinase (DNA-PK) that is currently being studied in phase I/II clinical trials. DNA-PK is essential for the repair of DNA-double strand breaks (DSB). Radiotherapy is frequently used in the palliative treatment of metastatic melanoma patients and induces DSBs. Melanoma cell lines and healthy-donor skin fibroblast cell lines were treated with CC‑115 and ionizing irradiation (IR). Apoptosis, necrosis, and cell cycle distribution were analyzed. Colony forming assays were conducted to study radiosensitizing effects. Immunofluorescence microscopy was performed to determine the activity of homologous recombination (HR). In most of the malign cell lines, an increasing concentration of CC-115 resulted in increased cell death. Furthermore, strong cytotoxic effects were only observed in malignant cell lines. Regarding clonogenicity, all cell lines displayed decreased survival fractions during combined inhibitor and IR treatment and supra-additive effects of the combination were observable in 5 out of 9 melanoma cell lines. CC-115 showed radiosensitizing potential in 7 out of 9 melanoma cell lines, but not in healthy skin fibroblasts. Based on our data CC-115 treatment could be a promising approach for patients with metastatic melanoma, particularly in the combination with radiotherapy.
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