New research by scientists at the Buck Institute for Research on Aging in Novato shows that rapamycin, a promising drug for an array of age-related diseases, can be effective when used only intermittently.
Results of the research, which included a contribution by Dr. Peter Nelson at the Fred Hutchinson Cancer Research Center in Seattle, was published Monday in the online edition of Nature Cell Biology.
It has been previously demonstrated that rapamycin can extend the life span of mice by as much as 14 percent. An immunosuppressant drug first approved for use by the U.S. Food and Drug Administration to help prevent organ rejection after transplants, rapamycin was later approved to treat cancer.
“What we’re excited about is the fact that we’ve found a mechanism where you don’t give the drug every day, which is going to be safer and even more efficacious with regard to not having severe side-effects,” said Buck professor Judith Campisi, senior scientist on the study.
Rapamycin can render some patients susceptible to opportunistic infections. Its use has also been associated with hyperglycemia, which can cause type 2 diabetes, and high levels of triglycerides in the blood, which play a role in causing heart disease.
“If I told you you need to take a pill every day from the time you are 40 until the day you die, you might have second thoughts about that,” Campisi said. “But if I said you just need to do it every five years you’d feel a lot better about it. The drug companies hate this idea, but we don’t work for the drug companies.”
In the study, the research team first used chemotherapy to treat mice with prostate cancer. The chemotherapy damages the mice’s DNA causing senescence, both to the tumor and surrounding cells. Senescence is the loss of a cell’s ability to divide and grow.
Next, the researchers gave the mice rapamycin. Even though the drug was administered intermittently, it suppressed the ability of the tumor cells to relapse in the mice.
Campisi said chemotherapy typically shrinks tumors in humans but inflames surrounding tissue. She theorizes that those inflamed cells secrete proteins that trigger residual cancer cells to grow again.
“What we discovered in our paper is that rapamycin is very good at reducing a certain type of inflation,” Campisi said. “My guess is there would be more success with rapamycin if the patients were chosen based on how inflamed their tumors are rather than how fast they grow, which is currently the criteria that is used.”
Dr. Nelson, an oncologist who specializes in treating prostate cancer, plans to test this theory with a clinical trial that combines rapamycin with standard treatments.
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