Old drug could be the new key to treating the deadliest form of lung cancer
Could an outdated drug be the key to treating small cell lung cancer, the deadliest form of lung cancer? According to a study in mice from researchers at Washington University School of Medicine in St. Louis, it may be so.
The new treatment uses cyclophosphamide; a drug once used to treat small cell lung cancer that was displaced in favor of platinum-based drugs in the 1980s.
One treatment option
"Small cell lung cancer has one treatment option -- platinum-based chemotherapy -- and that adds maybe two to six months of life," said co-senior author Nima Mosammaparast, MD, PhD, 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. These tumors are just massively resistant to just about everything. So what this study shows is that we can actually combine a new target with an old drug to reduce resistance and potentially make the treatment much better and give these patients a much better chance."
It all has to do with a protein called SMYD3 that is highly expressed in small cell lung cancer and some other cancers. Healthy lung tissue has very little SMYD3, which led the researchers to think that getting rid of the protein might target cancerous cells while sparing healthy ones.
To test this hypothesis, the researchers created mouse models of human disease by grafting cancerous cells from two people with small cell lung cancer. One set of cells came from a patient who had not yet been treated, so the cells had no chance of developing resistance. The other came from a patient who had been treated with and became resistant to standard platinum-based therapy.
A dual treatment
When the tumors in mice grew substantially enough, the researchers treated them with an inhibitor of SMYD3 and with cyclophosphamide. But inhibiting SMYD3 alone didn’t sufficiently slow down the growth of the tumors. Similarly, cyclophosphamide alone had weak results.
It initially halted the growth of tumors from both patients, but the tumors started to grow again after about two weeks. It was only the combination of the two drugs that stopped the tumors in their tracks, ensuring that they did not restart growing for the duration of the trials.
"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 drug. But the nice thing about this strategy is that it may work where current therapies have failed. This treatment worked just as well against the tumor from the patient who had already relapsed on platinum-based therapy as it did against the untreated patient. People with small cell lung cancer are in desperate need of better treatments, and I'm very excited about the possibilities here."
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