Abstract
Introduction: Most of those who get ovarian cancer will die from this cancer. Of the major types of ovarian cancer clear cell carcinoma is the most aggressive and chemoresistant type of epithelial ovarian cancer. Here the sensitivity of clear cell ovarian carcinoma to poly adenosine diphosphate [ADP-ribose] polymerase (PARP) inhibitors is tested. Methodology: Ovarian cancer cell lines were treated with the PARP inhibitors AG14361, Veliparib, or Olaparib alone or in combination with cisplatin, carboplatinum, doxorubicin, 5-fluorouracil (5-FU), gemcitabine and paclitaxel for 72 hours. The IC50 concentrations were calculated. Each experiment was replicated 10 times. Results: As single agents the PARP inhibition of ovarian cancer among serous, endometroid and clear cell ovarian cancer cell lines was similar. Clear cell ovarian cancer seemed particularly susceptible to chemo-sensitization by PARP inhibitors with paclitaxel, 5-FU, carboplatin, doxorubicin and/or cisplatin. Antagonism was seen with gemcitabine. Conclusion: PARP inhibitors are exceptional chemosensitizers of clear cell ovarian cancer to treatment with most standard chemotherapy agents.
Highlights
Most of those who get ovarian cancer will die from this cancer
(12) poly adenosine diphosphate [ADP-ribose] polymerase (PARP) inhibitors are treatment friendly as Olaparib and Veliparib both have the advantage of being available orally. [13, 14] Here we show the effective use of PARP inhibiters as chemosensitizers against clear cell carcinoma with taxane, platinum and other agents used to treat ovarian cancer
The ES-2 clear cell ovarian carcinoma was derived from a 47 year old African American female with low to moderate level resistance to cisplatin and doxorubicin
Summary
Most of those who get ovarian cancer will die from this cancer. Of the major types of ovarian cancer clear cell carcinoma is the most aggressive and chemoresistant type of epithelial ovarian cancer. The sensitivity of clear cell ovarian carcinoma to poly adenosine diphosphate [ADP-ribose] polymerase (PARP) inhibitors is tested. Results: As single agents the PARP inhibition of ovarian cancer among serous, endometroid and clear cell ovarian cancer cell lines was similar. Clear cell ovarian cancer seemed susceptible to chemo-sensitization by PARP inhibitors with paclitaxel, 5-FU, carboplatin, doxorubicin and/or cisplatin. Conclusion: PARP inhibitors are exceptional chemosensitizers of clear cell ovarian cancer to treatment with most standard chemotherapy agents. Many cancers are deficient in their ability to repair by homologous recombination due to deficiencies in BRCA1, BRCA2 and other enzymes needed in this repair pathway This leads to the accumulation of chromosomal damage and the death of cancer cells.
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