Potential targets for Ovarian Clear Cell Cancer therapy

Gerbrandij, M.D. (2016) Potential targets for Ovarian Clear Cell Cancer therapy. Bachelor's Thesis, Biology.

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Abstract

Ovarian clear cell carcinoma is a subtype of epithelial ovarian cancer. OCCC has a low response to platinum based chemotherapy, so new therapeutic strategies are desired. ARID1A is a subunit of the SWI/SNF complex and mutated in 50% of the OCCC cases. ARID1A regulates gene expression by controlling the gene accessibility. HNF1β, ER and WT1 are markers which can be used to diagnose OCCC. A potential target for OCCC therapy is the reduction of HNF1β. Another possibility is to target the ARID1A mutation. Since ARID1A is a loss of function mutation it is not directly targetable, but restoration of ARID1A inhibits cell survival and cell growth. ARID1A mutations often coexist with mutations in PIK3CA and PTEN, inhibition of PI3K/AKT pathway in which these transcription factors are involved also decrease cell growth and cell survival. Inhibition of KRAS is also interesting, but KRAS inhibition in low grade serous ovarian carcinoma did not show a decrease in tumorigenic effects. Between EZH2 and ARID1A an antagonistic link is found. This means that inhibition of EZH2 with GSK126 induces apoptosis is ARID1A mutated cells. PIK3IP1 is a target gene of ARID1A and EZH2, PIK3IP1 induces apoptosis. PIK3IP1 only becomes activated when EZH2 and ARID1A are not present in the cell. ARID1B is quite similar to ARID1A; presence of ARID1B in ARID1A mutated cells results in cell survival, which makes ARID1B an interesting target. Between TP53 and ARID1A a mutational exclusive relation is described. P53 stabilization in OCCC cells can induce apoptosis. So, several possible therapeutic targets are mentioned. Although for all of them further research is necessary.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 08:14
Last Modified:	15 Feb 2018 08:14
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/14294

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