A UR research team led by Director of the UR Center for RNA Biology Dr. Lynne E. Maquat has found that blocking a certain cellular quality-control mechanism called nonsense-mediated mRNA decay (NMD) can make chemotherapy more effective to treat of cancer.

NMD is a quality-control pathway responsible for protecting the cell from mistakes it might make when carrying out its DNA instructions. It prevents the production of abnormal proteins that could potentially cause disease. In fact, over a third of genetically-inherited diseases, and acquired diseases, are characterized by this NMD pathway.

What makes NMD particularly relevant to chemotherapy treatments is its role as a molecular “valve” that adjusts gene expression to different environments. In the presence of certain chemicals, NMD activity will decrease.

Maquat and fellow UR researcher Maximillian Popp have published a paper in the scientific journal “Nature Communications,” detailing their research with NMD and how it can affect a cancer’s response to chemotherapy.

Their research involved the use of doxorubicin, a drug used to treat a variety of cancers, and its effectiveness on breast cancer cells under different conditions. In the first condition, breast cancer cells were exposed to doxorubicin alone. In the second, breast cancer cells were simultaneously exposed to doxorubicin as well as an NMDI, a drug that attenuates the actions of NMD. Under the second condition, the breast cancer cells showed a greater response to the drug, e.g. more cancer cells were killed.

Even more effective was the pretreatment of the cancer cells with NMDI, followed by the application of doxorubicin. Cell death was particularly pronounced in this application. A possible explanation was that the pretreatment primed the cells to become more responsive to the drug. Weakening the NMD action prior to treatment allowed the environment in the cell to change enough so that it could react more rapidly to the doxorubicin.

Maquat and her fellow researchers do not yet have a full explanation of these observations, but it may already be possible to increase the efficacy of chemotherapy. Drugs already on the market are known to inhibit NMD, and using these in conjunction with chemotherapy could result in a better response by cancer patients.

In recognition of her work with NMD, Lynne Maquat received the 2015 Gairdner International Award. Informally known as the “Canadian Nobel,” it is the top prize for biomedical research from Canada.

She is the first scientist from upstate New York to receive the prestigious award. 82 of the previous 313 winners have gone on to receive a Nobel Prize in Physiology or Medicine.

Maquat took time to profess her goals of greater representation of women in science, “With this award, I hope to inspire other young people, especially girls, and especially young women, to think about a career in science. If you like being creative, if you like puzzles, you can become a scientist and think about problems that have significance to all of us.”

Davrenov is a member of

the class of 2017.

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