Can res: researchers found the cause of drug resistance in ovarian cancer

August 25, 2018 / BIOON / - resistance to cisplatin is still one of the main obstacles in the treatment of high-grade malignant ovarian cancer (hgsoc) Cisplatin can induce DNA cross-linking by inhibiting the replication of DNA polymerase to selectively kill cancer cells The single strand DNA (ssDNA) produced by delayed replication fork (RF) is bound and protected by heterotrimeric replication protein A (RPA), which can be used as a platform for recruitment and activation of replication stressors Photo source: defective cells in cancer research process will have a lot of ssDNA and excessive RPA recruitment, which will lead to the depletion of RPA pool, which will lead to the following consequences: inhibition of RPA dependent processes, such as nucleotide excision repair (NER); catastrophic consequences of blocking RF Recently, researchers from Montreal University, Laval University and Harvard University used a series of human hgsoc cell lines to study the effect of RPA availability on chemosensitivity The researchers found a significant link between the sensitivity of these cell lines to cisplatin and the inability to repair DNA through ner, especially in the S phase The defect in NER is the depletion of RPA caused by the abnormal activation of DNA replication starting point during replication stress The decrease of RPA efficiency promoted Mre11 dependent degradation of RF DNA in cell lines with high sensitivity to cisplatin It is worth noting that ectopic overexpression of RPA can eliminate defective S-phase ner, replication fork instability and cisplatin sensitivity In conclusion, the researchers found that RPA failure is the main determinant of cisplatin sensitivity in hgsoc cell lines Reference: Fran ç OIS B é Langer et al Replication protein A availability duration DNA replication stress is a major determination of cisplatin resistance in Ovan cancer cells, cancer research (2018) Doi: 10.1158/0008-5472.can-18-0618