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New treatment method: targeting hallmarks in testicular cancer

Lok, R (2012) New treatment method: targeting hallmarks in testicular cancer. Bachelor's Thesis, Biology.

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Testicular cancer is a common disease in man. Every year, 660 new cases of testicular cancer arise in the Netherlands alone. The curing number is 90%, which is unique for metastatic cancer. Treatment options are chemotherapy, whether or not combined with radiotherapy. The golden standard for chemotherapy is platinum-based chemotherapy. However, 10% of the testicular cancer patients is cisplatin resistant and for these patients there are no good treatment options available. The aim of this literary study is therefore to determine whether mew targets can be identified to cure testicular cancer. There are a number of proteins which can play a role in the oncogenesis of testicular cancer: k-Ras, Myc (L-Myc, N-Myc and C-Myc), Bcl-2, Mdm2, EGFR and cKit. k-Ras arise because of a substitution from valin to serine in k-Ras resulting in constitutive proliferation signalling. Myc up-regulation results in stimulation of transcription. Bcl-2 inhibits apoptosis and autophagy. Mdm2 inhibits the functioning of the p53 tumour suppressor gene. The EGFR and cKit stimulate down-stream signalling and therefore proliferation, whereas they both inhibit apoptosis. Different approaches are possible to target the various hallmarks of testicular cancer, varying from inhibition on the RNA level till dephosphorylation or simply inhibition of the receptor ligand. k-Ras can be inhibited by the use of oligonucleotides and RNA interference. The Myc oncogene can be inhibited by bromodomain targeting drugs, inhibiting homodimerization or inhibition of down-stream targets. Mdm2 can be inhibited by administrating its antagonist, nutlin 3A. Targeting Bcl-2 can be obtained by using a dephosphorylating agent, PP2A. Also by the use of antibodies, ribozymes and small molecule BH3 mimetics Bcl-2 inhibition is accomplished. For EGFR a lot of targeting methods are possible. Inhibition of EGF and TGF alpha by a monoclonal antibody is one possibility. Also, antibodies with toxic effect, tyrosine kinase inhibitors, antisense RNA, small interfering RNA and ribozymes are methods of inhibiting the EGFR down-stream signalling. cKit can be inhibited by a tyrosine kinase inhibitor. For some treatment methods, like RNA interference, clinical administration is not possible yet, but will be in the nearby future. Other drugs, like the tyrosine kinase inhibitors or antibodies with toxins, have already been clinical administrated. Thus,a wide range of new treatment options can be further explored for the treatment of cisplatin resistant tesicular cancer patients.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:48
Last Modified: 15 Feb 2018 07:48

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