New Drug Inhibits the Growth of Cancer Cells
upstart writes in with an IRC submission for Runaway1956:
New drug inhibits the growth of cancer cells:
We managed to establish a potential cancer drug that targets mitochondrial function without severe side effects and without harming healthy cells", explains Nina Bonekamp, one of the lead authors of the study. Mitochondria contain their own genetic material, the mitochondrial DNA molecules (mtDNA), whose gene expression is mediated by a dedicated set of proteins. One such protein is the enzyme "mitochondrial RNA polymerase", abbreviated to POLRMT. "Previous findings of our group have shown that rapidly proliferating cells, such as embryonic cells, are very sensitive to inhibition of mtDNA expression, whereas differentiated tissues such as skeletal muscle can tolerate this condition for a surprisingly long time. We reasoned that POLRMT as a key regulator of mtDNA expression might provide a promising target", says Nils-Goran Larsson, head of the research team.
[...] In collaboration with the Lead Discovery Center, a translational drug discovery organization established by Max Planck Innovation, the research team designed a high-throughput test method for identifying a chemical compound that inhibits POLRMT. The POLRMT inhibitor strongly decreased cancer cell viability and tumour growth in tumour-bearing mice, but was generally well tolerated by the animals. "Our data suggest that we basically starve cancer cells into dying without large toxic side effects, at least for a certain amount of time. This provides us with a potential window of opportunity for treatment of cancer", says Nina Bonekamp. "Another advantage of our inhibitor is that we exactly know where it binds to POLRMT and what it does to the protein. This is in contrast to some other drugs that are even in clinical use." With the help of ACUS Laboratories in Cologne and the Max Planck Institute for Biophysical Chemistry in Gottingen, the team identified the chemical binding site of the inhibitor and obtained structural information of the POLRMT-Inhibitor complex.
Journal Reference:
Nina A. Bonekamp, Bradley Peter, Hauke S. Hillen, et al. Small-molecule inhibitors of human mitochondrial DNA transcription, Nature (DOI: 10.1038/s41586-020-03048-z)
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