Caused by a mutation that inactivates the tumor suppressor gene LKB1, PJS causes gastrointestinal polyps that have a 30 to 50 percent chance of becoming cancerous, says senior author Lewis Cantley, PhD, chief of the Division of Signal Transduction at Beth Israel Deaconess Medical Center (BIDMC) and a member of the Department of Systems Biology at Harvard Medical School.
Research conducted by Cantley’s laboratory on two other genetic conditions with symptoms similar to PJS had found that the diseases involved defects in the regulation of a protein called mTOR, so the researchers decided to look for a link between LKB1 and mTOR.
As predicted, they found that mouse cells lacking LKB1 and cells from PJS mouse polyps showed the activation of molecules known to be downstream of the mTOR protein.
“We knew that the drug rapamycin [commonly used to prevent newly transplanted organs from being rejected] could block mTOR,” says Cantley. “These new results suggest that the use of mTOR inhibitors, including rapamycin analogs currently being tested in clinical trials for the treatment of cancers and tuberous sclerosis, may be useful for the treatment of polyps arising in PJS patients, and possibly in other tumors that result from the sporadic loss of LKB1.”