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Novel radiosensitization strategies in cancer
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
2024 (English)Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
Abstract [en]

The aim of this thesis was to investigates the potential of using Onalespib (AT13387) and KRIBB11 in combination with radiotherapy as a novel treatment approach for head and neck cancer (HN), squamous cell carcinoma (SCC) and glioblastoma. Current clinical therapies for these cancer types have limitations, including resistance and unwanted side effects that reduce the quality of life and the likelihood of long-term survival. Radiation is often used in the treatment of HN+SCC and brain tumors, but the addition of novel drugs could eradicate resistant cells and may reduce toxicity due to dose reduction while keeping the efficacy. To evaluate cell lines’ survival, cell based assays such as colony formation, migration, and spheroids were used. Western blot was performed to determine key protein expressions in drug and radiation treated samples. Cell cycle analysis was performed by flow cytometry. Confocal microscopy was used to analyze DNA damage. U87 and U343 glioblastoma cell lines displayed decreased cell survival, arrested cell cycles and increased DNA damage from combination treatment of radiotherapy and Onalespib treatment. SCC cell line A431 and HN cell line SCC-25 showed decreased colony formation for combination therapy (radiotherapy+Onalespib+KRIBB11) and all tested HN+SCC cell lines displayed less migration in cells treated with all therapies combined. The study found conclusive evidence of synergistic effects of radiotherapy and Onalespib on all tested cell lines. The results for the combination therapy in the HN+SCC cell lines showed variations in efficacy and cell survival mainly due to KRIBB11. Combination treatments are a promising strategy to overcome resistance and improve treatment outcomes, however more studies are needed to further improve combination therapies as potential treatment for cancer.

Place, publisher, year, edition, pages
2024. , p. 37
National Category
Cancer and Oncology Cell Biology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-521708OAI: oai:DiVA.org:uu-521708DiVA, id: diva2:1831654
Educational program
Master Programme in Biology
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Available from: 2024-02-01 Created: 2024-01-26 Last updated: 2024-02-01Bibliographically approved

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CiteExportLink to record
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