By Janet Fang
Posting in Cancer
Pancreatic tumors are so drug-resistant because of the tough matrix of cells that surround them. By melting the sugar molecules in that barrier, an enzyme helps chemo drugs penetrate cancer cells.
By injecting a molecule that melts the tough structure around a pancreatic tumor, researchers have boosted standard chemotherapy, helping the drugs penetrate and better destroy cancer cells.
In a mouse model of pancreatic cancer, the treatment resulted in the longest survival seen. And this is already being tested in people. ScienceNOW reports.
Pancreatic tumors are one of the deadliest and most drug-resistant cancers. People diagnosed with the most common form – pancreatic ductal adenocarcinoma (PDA) – don’t usually respond to chemotherapy, living only a few months.
Researchers suspect that the tumors are enmeshed in a tough matrix of cells and molecules, called the stoma. This creates fluid pressure within the tumor that’s much higher than in the tumor’s blood vessels – making it harder for any drugs to get from the blood into the tumor.
(The pressure in those tumors are comparable to the pressure being pumped within the heart!)
So, a group led by Sunil Hingorani of the Fred Hutchinson Cancer Research Center in Seattle looked for a way to lower the pressure so that drugs can breach the barrier.
"Maybe not enough of the drug got into the tumor," Hingorani says.
- There’s an abundance of a sugar molecule in the stroma of PDA tumors. So the team treated mice with an enzyme called PEGPH20 (pictured) that degrades that particular sugar.
- Pressure in the tissue around the tumor began to drop. By 24 hours, the level was like that of normal pancreas tissue. When the tumors were cut out, they were soft and pink – and no longer hard and white like the way were before the enzyme.
When mice with PDA tumors were injected with PEGPH20 along with the standard drug for pancreatic cancer, they lived 70% longer than mice receiving the drug alone. They also developed fewer metastases.
A formulation of the PEGPH20 enzyme has already been approved for a different drug-delivery application. Now, a trial to test the combination of the enzyme with the pancreatic cancer drug is under way by Halozyme Therapeutics.
The work was published in Cancer Cell today.
Image: PEGPH20 degrading the protective matrix / Halozyme
Mar 20, 2012