Lesser-known DNA Repair Process May Be Therapeutic Target in Certain Breast Cancers, Study Says

Lesser-known DNA Repair Process May Be Therapeutic Target in Certain Breast Cancers, Study Says
Some breast cancers with mutations in DNA damage repair genes may rely on a DNA repair enzyme called polymerase theta for survival, a new study shows, suggesting that blocking this enzyme or its associated pathways could be a therapeutic strategy to treat these breast cancers. The study, "Genetic determinants of cellular addiction to DNA polymerase theta," was published in Nature Communications. Sometimes, the DNA in cells becomes damaged, whether because of toxins or the normal wear and tear of replication. Cells have numerous molecular mechanisms to deal with this, broadly termed the DNA damage response (DDR). Many cancer cells have deficits in some of these processes. For example, the BRCA genes are involved in DNA repair, which is why cells that lack functional BRCA genes are more likely to develop mutations and, therefore, become cancerous. A lesser known part of the DDR is theta mediated end joining (TMEJ), a process named for the central enzyme, DNA polymerase theta (encoded by the gene POLQ). This pathway is relatively error-prone, and it is thought to play a minor role in DNA repair in normal cells, which can generally survive without POLQ. However, previous studies have shown that TMEJ is essential for the survival of cancer cells that lack certain other components of the DDR, such as BRCA. This finding raised the possibility that blocking TMEJ could be used therapeutically to treat breast cancers lacking BRCA. In the new study, researchers conducted a screen to look for other genes whose mutations could render cells sensitive to inhibitors of DNA polymerase theta. Conceptually, this involved removing certain genes from the cells' genome, and looking for those that led to cell death when POLQ was also lacking. Out of 309 genes associ
Subscribe or to access all post and page content.