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Combining EGFR inhibitors with chemo- and radiotherapy in lung cancer treatment

Katoen, F.M. (2009) Combining EGFR inhibitors with chemo- and radiotherapy in lung cancer treatment. Bachelor's Thesis, Biology.

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Abstract Lung cancer is the leading cause of cancer death and leads approximately to 1.18 million deaths each year worldwide. Chemotherapy, radiotherapy, antibodies and small molecules are clinically used to treat lung cancer. Chemo- and radiotherapy trigger apoptosis through provoking an enormous amount of DNA damage. Antibodies and small molecules work on the epidermal growth factor receptor (EGFR), a cell surface receptor involved in cancer development and progression. Antibodies, which are used to inhibit epidermal growth factor receptor signaling, work on the extracellular domain of the EGFR. Antibodies bind to the ERF receptor to block the binding of epidermal growth factor (EGF), which inhibits the normal function of the EGFR such as cell proliferation, angiogenesis, invasion, metastasis, blocking of differentiation and apoptosis inhibition. Small molecules, which are also used to target the EGFR, work both on the extracellular and intracellular domain of the EGF receptor. Extracellularly, the small molecules bind to the EGFR to block the activation of the EGF receptor. Intracellularly, small molecules compete with ATP in binding to the tyrosine kinase domain of the EGF receptor. Binding of small molecules to the tyrosine kinase domain leads to inhibition of cell proliferation, angiogenesis, invasion and metastasis; because the kinase domain does not become activated by ATP and can no longer exert its function. Because none of these treatments work efficiently in all lung cancer patients, combined treatments become a substantially interest. The most promising therapy is the Cetuximab antibody combined with chemo- and radiotherapy. It is shown that this combination is effective, although the mechanism behind this improved effect is still uncertain. In this literature thesis I will discuss a number of mechanisms that may explain the improved effect of Cetuximab combined with radio/chemotherapy. First, I will discuss the influence of membrane composition on EGFR and checkpoint signaling. Second, the effect of DNA damage on EGFR levels will be analyzed. Third, I will discuss cell cycle kinetics in response to EGFR inhibition. Finally, the intracellular trafficking of the EGFR will be analyzed. In conclusion, I will discuss potential molecular mechanisms of EGFR inhibition combined with chemo- and radiotherapy.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:28
Last Modified: 15 Feb 2018 07:28

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