Drugs Combinations

Subject : Science and Technology

Section: Biotechnology

The enzyme PRMT5 is broadly overexpressed in many cancer cells. Therefore, targeting the PRMT5 enzyme with drugs in combination with low dosage camptothecin will help in killing cancer cells more effectively.
The PRMT5 enzyme, which is found in abundance in cancer cells, directly regulates the natural cellular repair mechanisms through chemical fine tuning. This results in repairing of DNA breaks generated by camptothecin and thus, resistance to chemotherapy.

Major breakthrough

In 2018, Researcher achieved a breakthrough with the identification of the DNA repair proteins TDP1 (Tyrosyl DNA phosphodiesterase 1) and PRMT5 binding which was published in Nucleic Acids Research. But at that time, they did not understand the mechanism of action. Continuous research in the last five years helped unravel the mechanism in detail and the implications of a combinatorial chemotherapy.
PRMT5 inhibitor, GSK3326595, has been approved as a mono therapy in phase IIclinical trials of cancer. Therefore, the latest work provides a new rationale for using the combination of Top1-PRMT5 inhibitors in tumorigenesis.