Drug combo therapy in mice blocks drug resistance, halts tumor growth WUSTLmedschool nature
—and that adds maybe two to six months of life," said co-senior author Nima Mosammaparast, MD, Ph.D., an associate professor of pathology & immunology and of medicine at Washington University, and a researcher at Siteman Cancer Centerat Barnes-Jewish Hospital and Washington University School of Medicine."The problem is that these tumors respond to treatment initially, but then they come back. This has not changed for 30 years.
The study came together fortuitously. Co-senior author Nicolas Reynoird, Ph.D., a professor at Grenoble Alpes University, studies how internal signaling within cells—and deregulation of such signaling—can lead to cancer progression and drug resistance. A few years ago, his team discovered that a protein called RNF113A may play a role in small cell lung cancer, but the researchers could not determine what the protein does. Meanwhile, Mosammaparast was studying how cells repair injured DNA.
The team discovered that RNF113A is regulated by a protein called SMYD3 that is highly expressed in small cell lung cancer and some other cancers. High levels of SMYD3 are associated with more invasive disease, increased resistance to alkylating chemotherapy and worse prognosis. Healthy lung tissue has very little SMYD3, which led the researchers to think that knocking it down might targetSo they tried it.
All of the mice grew tumors. When the tumors were big enough, the researchers treated the mice with an inhibitor of SMYD3, cyclophosphamide, both or an inactive solution. Inhibiting SMYD3 alone modestly slowed down the growth of the tumors. Cyclophosphamide initially halted the growth of tumors from both patients, but the tumors started to grow again after about two weeks, indicating that they had developed resistance. However, the combination of the two drugs stopped the tumors in their tracks.
"We're talking to a number of other groups about starting a phase 1 clinical trial as soon as possible," Mosammaparast said."One of the challenges we will face is convincing doctors to go back to an old
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