Scientists studying about two rare inherited cancer syndromes suggested new treatment methods for the same, according to a report published on July 17, 2018.
This study was conducted by the scientists at the Yale Cancer Center (YCC). They found that cancers are caused due to the breakdown in how cells repair their DNA. The two conditions, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) and Succinate Dehydrogenase-related Hereditary Paraganglioma and Pheochromocytoma (SDH PGL/PCC) are found to increase the risk of tumors that may be benign or cancerous.
Abnormally large amounts of metabolites are produced by cells in both inherited cancer syndromes. These metabolites are part of the biochemical process, which is used by the body to turn carbohydrates, fats, and proteins into energy. It was found that the high levels of metabolites is capable of degrading a process known as homologous recombination. The damage that occurs when cells divide is mended by the cells through this process.
PARP (poly ADP-ribose polymerase) inhibitors are designed for killing cancer cells that have already lost some of their ability to repair their DNA via homologous recombination. The inhibitors try to stop the process of DNA repair by cancer cells completely, resulting in killing of the cell. The Food and Drug Administration (FDA) has approved three such drugs to treat breast, ovarian, and other types of cancers with mutations in BRCA genes that disrupt homologous recombination.
Parker Sulkowski, lead author of the paper said, “Our research is identifying additional biomarkers for tumors that are sensitive to PARP inhibitors, which will be helpful to the field.” On analyzing these sample tumors, defects were found in DNA repair. Furthermore, researchers performed experiments in various kinds of human cells that model the two inherited syndromes. These studies demonstrated that the two metabolites could suppress the homologous recombination pathway and leave the cells sensitive to PARP inhibitors.