Chemotherapy causes cancer cells to become senescent which is associated with increased resistance to standard-of-care cancer therapies. Senescent cells stop dividing but remain metabolically active. Moreover, senescent cancer cells secrete mediators that increase inflammation and modulate tumour microenvironment cells. Chemotherapy also causes senescence in normal cells of patients receiving these therapies. This affects the immune responses of these patients and creates metastatic niches that can promote cancer progression. Senolytics are a new class of drugs that kill/remove senescent cells but their application in the treatment of cancer is unknown. This PhD will evaluate the pharmacology of treating cancer senescent cells with senolytics while also elucidating the underlying tumour characteristics associated with a good/poor response to these drugs.
In this PhD, we will employ routine cell and molecular biology techniques to study senolytic drug responses in cancer cell models. You will gain experience in RNAi and protein over-expression techniques, the study of intracellular signalling and a variety of in vitro assays to measure key hallmarks of tumorigenesis and drug responses in cancer cells and tumour microenvironment immune cells. Novel results will be tested in in vivo models and/or clinically relevant samples.
The project will provide hands-on training for the student in the following:
•Cancer cell culture/co-cultures
•Real time monitoring of cell proliferation
•Real time monitoring of cell migration
•Assays to measure cell viability and apoptosis
•Protein, RNA and DNA isolation methods
•a thorough understanding of cancer biology
•Novel techniques of gene silencing and gene knock out
•Protein over-expression techniques
•Protein detection methods
Working as a PhD will also provide the following training:
•Oral and poster presentation skills
•Working as part of a team
•Project management: Planning and organising experiments, time management
This research aims to develop strategies to develop a stratification biomarker for the use of senolytic therapy in the treatment of ovarian cancer.
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