Researchers have developed an antibody that they say can stop an enzyme which helps some breast cancers spread.
With further development, the antibody developed by researchers at the Cold Spring Harbor Laboratory in the US may offer an effective drug treatment for breast cancers.
The antibody, described in the journal Genes & Development, targets an enzyme called PTPRD that is overabundant in some breast cancers.
PTPRD belongs to a family of molecules known as protein tyrosine phosphatases (PTPs), which help regulate many cellular processes.
They do this by working in concert with enzymes called kinases to control how other proteins inside cells behave. Kinases add small chemical regulators called phosphates to proteins. PTPs take them off.
Disruptions in the addition or removal of phosphates can contribute to inflammation, diabetes, and cancer. Some disruptions can be corrected with kinase-blocking drugs, the researchers said.
People have targeted kinases for 25, 30 years. It is a multibillion-dollar industry. But many challenges remain. In cancer, patients will respond to these sorts of kinase inhibitors and then, after a period of time, resistance develops,” said Professor Nicholas Tonks from Cold Spring Harbor Laboratory.
Drugs that control PTP activity could have a major impact on human health. However, such drugs have been difficult to develop.
To stop PTPRD activity, Zhe Qian, a graduate student at Cold Spring Harbor Laboratory, devised a new kind of PTP blocker. He targeted the enzyme with a synthetic antibodya molecule that recognises and binds to its target in a particular fashion.
PTPRD molecules sit nestled in the outer membranes of cells, with bits protruding inside and out.
Qian designed his antibody to grab onto two PTPRD molecules from outside a cell simultaneously.
The researchers then showed that when the antibody binds to its target, it draws pairs of PTPRD proteins together into an inactive configuration.
This not only prevents PTPRD from working but also leads to the protein’s destruction, they said.
The team has shown that once this happens, breast cancer cells growing in the lab become less invasive.
The researchers said the same strategy might be used to block the possible metastasis-promoting enzyme in patients with breast cancer.
This might be particularly effective when combined with a kinase-targeting drug, they added.
