New York [US]: Professor Nicholas Tonks’ laboratory identified an antibody that can suppress an enzyme that may aid in the spread of some breast tumours. With more research, the antibody may be able to provide a feasible therapeutic treatment for the same breast cancers.
The novel antibody targets PTPRD, an enzyme that is overexpressed in some breast tumours. PTPRD is a member of the protein tyrosine phosphatase (PTP) family of molecules, which aid in the regulation of numerous cellular functions.
They accomplish this by collaborating with enzymes known as kinases to regulate the behaviour of other proteins within cells. Kinases are enzymes that add tiny chemical regulators known as phosphates to proteins. PTPs remove them.
Disruptions in the addition or removal of phosphates can contribute to inflammation, diabetes, and cancer. Some disruptions can be corrected with kinase-blocking drugs.
‘People have targeted kinases for 25, 30 years,’ Tonks explains. ‘It’s 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.’
Drugs that control PTP activity could have a major impact on human health. However, such drugs have been difficult to develop. Tonks has studied PTPs since he discovered them as a postdoctoral researcher. He calls the enzymes ‘an untapped resource for drug development.’
Many enzymes can be switched off with small molecules designed to latch onto and block the part of the enzyme that carries out its work. But that won’t work for PTPs like PTPRD. So, alternative strategies are necessary.
To stop PTPRD activity, graduate student Zhe Qian devised a new kind of PTP blocker. He targeted the enzyme with a synthetic antibody–a molecule that recognizes 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.
Qian and colleagues in the Tonks lab 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. The team has shown that once this happens, breast cancer cells growing in the lab become less invasive.