One step closer to precision cancer therapies
- July 31, 2022
- Posted by: OptimizeIAS Team
- Category: DPN Topics
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One step closer to precision cancer therapies
Subject : Science and Technology
Section: Biotechnology
- Research found a combination of molecules that can be used for developing novel anti-cancer therapeutics
- Research work over the last decade has helped identify a new target for killing cancer cells, opening the door for potential new therapy. The target pathway is utilised by cancer cells to repair DNA double-stranded break repair
Preventing DNA Replication
- Topoisomerase 1-targeted chemotherapy is one of the mainstays of treating cancer cells. Currently-used anti-cancer drugs (Camptothecin, Topotecan and Irinotecan) target a molecule (the enzyme Topoisomerase 1 or Top1) involved in DNA replication. While DNA replication is essential to cell division, runaway replication characterises cancer.
- Research found that cancer cells sometimes develop resistance to Topoisomerase 1-targeted chemotherapy through their intrinsic DNA repair toolbox. Based on these insights, a combination of molecules (the protein PRMT5, and the enzyme TDP1) can be used as potential targets for developing novel anti-cancer therapeutics, thus taking us a step closer to developing precision medicine approaches for cancer patients.
- Top1, an enzyme in all higher eukaryotes, is essentially responsible for relaxing DNA as it coils during replication (and transcription). The drugs directed at this pathway disrupt the activity of Top1 by changing its shape and rendering it ineffective. While these result in a significant amount of cell death, including cancer cells, natural cellular repair mechanisms (using TDP1) often kick in and counteract the action of the drug.
- Researcher developed CRISPR-mediated knock-out cells where the PRMT5 (Protein arginine methyltransferase 5) enzyme in the cells is no longer present. When challenged with a low dosage of camptothecin which is below the toleration levels used in chemotherapy, they found that the cancer cytotoxicity increased markedly. This helped confirm that PRMT5 deficiency in the cell is the target of the camptothecin.