de Jong, I.E. (2009) DNA damage repair in cancer therapy. Bachelor's Thesis, Biology.
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Abstract
Cells have two systems essential for maintaining the genome integrity of a cell population: DNA repair and apoptosis. Mutations in each of these systems can cause cancer. This literature thesis focuses on aberrations in the DNA damage repair, that causes an increase in the risk of cancer. In single strand break (SSB) repair, the major difference between the pathways, is the type of damage that is recognized, and how it is recognized. However, in DSB repair the major differentiate is in their fidelity of repair. homologous recombination (HR) uses a (nearly) identical template to repair DSBs, while non-homologous end-joining (NHEJ) anneals lose ends without the use of a template. NHEJ is therefore a error-prone pathway. In each repair pathway can occur mutations which goes along with loss of function of a repair pathway. When a repair pathway is heterozygous mutated in healthy cells and homozygous mutated, inducing loss of function, in tumor cells, it is possible to injure cancer cells to a greater extent than healthy cells. The loss of function from one repair pathway in de tumor, can result in an increased cytotoxic effect of DNA damage to cancer cells. However, the cytotoxic effect of DNA damage can be enlarged by inhibition of a second repair pathway. By inhibiting a SSB repair machinery, the remaining SSB are converted to DSB after replication. In cancer known to have loss of function mutations in DSB repair, cancer therapy is possible by inhibition of a SSB repair. Consequently, the damages can be repaired in DSB repair in healthy cells, while tumor cells accumulate DSBs. The use of such targeted therapy can be combined with DNA damage inducing agents like chemo- or radiotherapy, in which success of the therapy depends on whether or not the cancer cell survive the therapy. By disengaging a large part of the DNA repair, cancer cells will be unable to restore the acquired damage and go into apoptosis. This literature thesis will discuss mutations that are known to impair DNA repair, especially mutations in the HR repair pathway.
| Item Type: | Thesis (Bachelor's Thesis) |
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| Degree programme: | Biology |
| Thesis type: | Bachelor's Thesis |
| Language: | English |
| Date Deposited: | 15 Feb 2018 07:29 |
| Last Modified: | 15 Feb 2018 07:29 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/8771 |
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