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Thesis: Testicular germ cell tumours: why so sensitive?

Noordink, A.M. (2017) Thesis: Testicular germ cell tumours: why so sensitive? Bachelor's Thesis, Biology.

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The incidence of testicular cancer, that is the most frequent solid malignant tumour in young men, is still increasing. Despite the rising number of patients diagnosed with this kind of cancer, the curability of this tumour is high due to effective cisplatin-based treatment. Still there is a small group of patients that is resistant to this therapy, but the underlying mechanism(s) behind this resistance is not clear. This thesis will give an overview of the current ideas and research that is done in this field in the past decades till very recently. Ranging from targets and factors upstream or downstream the apoptosis induction pathways in testicular cancer. The keyplayer in this overview is p53, because p53 is shown to be important in intrinsic and extrinsic apoptosis induction after chemotherapeutic treatment. Regulation of p53 by MDM2 is shown to influence this sensitivity and inactivation of p53 decreases this sensitivity. Another possible mechanism for this sensitivity is the mitochondrial priming proximity of the cell. When the cells are highly primed, the pro-apoptotic proteins are more abundantly expressed, causing the cell to go into apoptosis more easily. Resistance to cisplatin treatment can be caused by various reasons, including deficient mismatch repair, induction of differentiation, loss of function of p53, epigenetic alterations, overexpression or activation of the PI3K/pAKT pathway and decreased expression of pluripotency markers like Oct-4 and Noxa. Nowadays BH3 mimetics, that bind the anti-apoptotic factors, are already used in acute myeloid leukemia and may be promising for testicular cancer as well. Besides this, further research and clinical trials need to be done to bring phosphorylating kinases like AKT or PI3K inhibitors or other possible targets that can decrease the resistance to the clinic and to cure all testicular cancer patients.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:27
Last Modified: 15 Feb 2018 08:27

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