2008 Woodie Awards
Receptor serves as marker, target for pancreatic cancer
Issue date: 10/9/08
Hopkins scientists, in a research article recently published in the Journal of Proteome Research, have found a marker for pancreatic cancer that could be targeted to cure the disease. A team led by Akhilesh Pandey and Manuel Hidalgo of the School of Medicine found aberrantly activated growth factor receptors - proteins that receive signals telling a cell to grow and multiply - to be a factor in pancreatic cancers.
Growth factor receptors promote cell growth and division when activated by a chemical from outside the cell. In pancreatic cancer, like other cancers, cells malfunction, multiply and spread throughout the body. "Aberrant activation of signaling pathways is suspected to be the root cause … in most cancers," Pandey said. But which pathway to target?
The goal of the experiment was to find "markers that will make a pancreas cancer vulnerable" to drugs that inhibit or block specific growth factor receptors, according to Hidalgo. To find these markers, researchers looked for kinases - proteins involved in activating specific growth factor receptors - in mice injected with pancreatic cancer. The group found activated epidermal growth factor receptor (EGFR) in a line of pancreatic cancer-infected cells they grew.
"Only those tumors in which EGF receptor signaling was abnormally high responded to drugs that inhibit the activity of this receptor, while the others did not," Pandey said.
The findings were straightforward: "Activated EGFR is the key marker," Hidalgo said.
It might seem surprising that some pancreatic cancer tumors did not respond to blocking the EGFR. But that just means there is more complexity to discover. "Cancers that carry the same diagnosis are not all identical at the molecular level," Pandey said, so it is likely that only some pancreatic cancers use EGFR to grow and spread.
Blocking the EGFR is a common treatment for some cancers, such as lung cancer, so clinical trials are being conducted to treat pancreatic cancer with EGFR inhibitors. "The patients recruited for these studies are generally not selected on the basis of EGF receptor activation," according to Pandey, so the EGFR inhibitors will only treat the patients with excessive EGFR activation, and will thus appear to work poorly at best when looking at the population as a whole.
Group findings show patients need to be screened for excessive EGFR activation, so patients without this marker - who probably have a different form of pancreatic cancer - are spared from what would likely be an unsuccessful treatment.
Screening patients for excessive EGFR activation would also improve clinical trial results, since only patients who have pancreatic cancers that use activated EGFR would receive a treatment that blocks the EGFR. This would allow new medicines targeting specific varieties of pancreatic cancer to pass clinical trials faster, so people with those cancers might be cured sooner.
Growth factor receptors promote cell growth and division when activated by a chemical from outside the cell. In pancreatic cancer, like other cancers, cells malfunction, multiply and spread throughout the body. "Aberrant activation of signaling pathways is suspected to be the root cause … in most cancers," Pandey said. But which pathway to target?
The goal of the experiment was to find "markers that will make a pancreas cancer vulnerable" to drugs that inhibit or block specific growth factor receptors, according to Hidalgo. To find these markers, researchers looked for kinases - proteins involved in activating specific growth factor receptors - in mice injected with pancreatic cancer. The group found activated epidermal growth factor receptor (EGFR) in a line of pancreatic cancer-infected cells they grew.
"Only those tumors in which EGF receptor signaling was abnormally high responded to drugs that inhibit the activity of this receptor, while the others did not," Pandey said.
The findings were straightforward: "Activated EGFR is the key marker," Hidalgo said.
It might seem surprising that some pancreatic cancer tumors did not respond to blocking the EGFR. But that just means there is more complexity to discover. "Cancers that carry the same diagnosis are not all identical at the molecular level," Pandey said, so it is likely that only some pancreatic cancers use EGFR to grow and spread.
Blocking the EGFR is a common treatment for some cancers, such as lung cancer, so clinical trials are being conducted to treat pancreatic cancer with EGFR inhibitors. "The patients recruited for these studies are generally not selected on the basis of EGF receptor activation," according to Pandey, so the EGFR inhibitors will only treat the patients with excessive EGFR activation, and will thus appear to work poorly at best when looking at the population as a whole.
Group findings show patients need to be screened for excessive EGFR activation, so patients without this marker - who probably have a different form of pancreatic cancer - are spared from what would likely be an unsuccessful treatment.
Screening patients for excessive EGFR activation would also improve clinical trial results, since only patients who have pancreatic cancers that use activated EGFR would receive a treatment that blocks the EGFR. This would allow new medicines targeting specific varieties of pancreatic cancer to pass clinical trials faster, so people with those cancers might be cured sooner.
Be the first to comment on this story