Here is another article in our series about things going on around Rochester.
Cancer is an extremely common problem across the United States. For example, research shows that more than 3.5 million nonmelanoma skn cancers alone are diagnosed in more than two million Americans every year, to say nothing of melanoma or even other forms of cancer. Fortunately, a team at the University of Rochester may have found a way to better treat many cases of this common disease: by stopping a cellular quality control mechanism called NMD (nonsense-mediated mRNA decay), the researchers believe they can make chemotherapy more effective.

Led by Dr. Lynne E. Maquat, director of the Center for RNA Biology at the University of Rochester, the research team has spent several years studying the role of NMD, which the researchers describe as the body’s way of proofreading RNA or mRNA, nucleic acid that delivers instructions from DNA and uses it to create proteins to carry out bodily functions. NMD checks these messenger molecules and derails the production of unwanted proteins that can disrupt normal processes and initiate disease. However, over the last several years, Maquat’s team and other researchers have discovered that NMD also helps cells adjust to changes in their environment and respond rapidly to certain stimuli.

Given these roles, one of the team members, Maximilian Popp, conducted a study in which he exposed breast cancer cells to doxorubicin, a drug used to treat leukemia, breast, bone, lung and other cancers, before measuring their viability. Next, he simultaneously treated cells with doxorubicin and another compound that inhibits NMD. Finally, he treated cells with the compound that inhibits NMD, removed the compound after a few hours, and then treated cells with doxorubicin.

Popp found that the third treatment regimen was the most effective: cells were 2.5 times more likely to die when compared to doxorubicin alone. The research team isn’t entirely sure why this strategy works, but Maquat and Popp both speculate that blocking NMD primes the cells for apoptosis, or cell death, by boosting the activity of genes that respond to the cellular stress caused by chemotherapy. However, they noted that the NMD works with the doxorubicin to help promote apoptosis.

The research team admits that their work is in the early stages and will take some time before it can be applied to human treatments. However, Popp, a Howard Hughes Medical Institute fellow supported by the Damon Runyon Cancer Research Foundation, says that their findings support combining drugs that inhibit NMD with chemotherapy.