The hormone somatostatin may be effective in treating some patients with pancreatic cancer, new research suggests. Studies conducted in mice and in laboratory samples found that pancreatic tumors responded to somatostatin only if the tumor cells had receptors for the hormone.
The hormone somatostatin may be effective in treating some patientswith pancreatic cancer, new research suggests. Studies conductedin mice and in laboratory samples found that pancreatic tumorsresponded to somatostatin only if the tumor cells had receptorsfor the hormone.
It is not known how many patients might have a form of pancreaticcancer with these receptors, said William Schirmer, coauthor ofthe study and assistant professor of surgery and a member of OhioState University's Comprehensive Cancer Center. But, he said,future research should look into the issue.
This is the first study to show a possible role for somatostatinreceptors in pancreatic cancer, the fourth leading cause of cancerdeath in the United States. Only about 2% of patients are alive5 years after diagnosis, and there are no effective treatmentsfor the disease.
Several small clinical trials at individual medical centers havetested the use of somatostatin to slow or prevent the recurrenceof pancreatic cancer following surgery. Those trials, however,have shown that somatostatin does not prolong the lives of patientswith pancreatic cancer.
"I'm not surprised by those results," said Schirmer."Those studies did not look at whether the tumors in thosepatients showed the presence of somatostatin receptors."
"Our data suggests that there may be a minority of patientswho would benefit from somatostatin therapy. But I think thesepatients are being missed because the trials haven't identifiedwhich patients have the receptors." Schirmer and a team ofresearchers presented their data at the American College of Surgeonsmeeting in October and at the Association for Academic Surgeonsin November.
Presence of Somatostatin Receptors an Important Determinantof Response
It is possible that somatostatin could inhibit tumor growth indirectly.It could inhibit the production of a growth factor or hormonethat stimulates tumor growth, for example.
But Schirmer's work suggests that the presence of receptors isthe single most important factor in determining whether a tumorresponds to treatment with somatostatin, which is often consideredan antigrowth hormone.
The researchers studied the effect of somatostatin on human pancreaticcancer cells growing in the laboratory and later in animals. Outof 10 different pancreatic cancer cell lines, only 1 respondedto somatostatin. It was also the only cell line with receptorsfor the hormone.
The researchers then went back and studied each cell line moreclosely. They have done a detailed characterization of 6 of the10 cell lines so far.
They looked, for example, at whether somatostatin slowed the growthof the cells growing in culture. They found that while somatostatinhad no effect on the cancer cells without receptors, it couldslow the growth of cancer cells with receptors by as much as 20%.
The researchers also used the cells to grow tumors in mice. Theyhave transplanted six of the cancer cells into groups of 20 mice,10 of which were treated with somatostatin. After 36 days, theresearchers measured the size of the tumors.
Tumors from mice with somatostatin receptors were half the sizeof those of the controls (which did not receive somatostatin).In mice with tumors that lacked the receptors, there was no significantdifference in tumor size between the somatostatin-treated miceand control animals.
"We're not to the point where we can say that the receptorstudies on the human cell lines is going to predict a response,"said Schirmer, "but I think we can say that receptor analysisshould be considered in future studies to help explain the resultsof clinical trials using somatostatin for pancreatic cancer."
Clinical Trials Planned
Schirmer notes that if only 5% of people with pancreatic cancerhave the receptor, for example, it means that, on average, 80out of 100 patients in a clinical trial wouldn't respond to somatostatin,"and the treatment will be deemed a failure when looked atstatistically," he said.
"But what if the patients with receptors have a good response?We need to be able to sort that out so we can say from the studythat, although somatostatin doesn't work in 80% of patients, itdoes work in those who do have the receptors."
Schirmer is planning a clinical trial at Ohio State that willdo just that. The beginning of that trial is months away, however.
The research group is also studying pancreatic tumors removedduring surgery for the presence of somatostatin receptors. Theyare correlating them with scintigraphy scans that use a radioactiveform of somatostatin. This could provide a nonsurgical means ofdetermining whether somatostatin receptors are present in a patient.