A new discovery has been reported by a team of researchers that will lead to the development of new way to tackle aggressive breast cancer.
The breast cancer subtype in question is commonly called "HER2-positive"; it's a subset of the disease affecting about one patient in four, in which tumor cells overexpress a signaling protein called HER2.
The blockbuster drug Herceptin is a treatment of choice for many women with HER2-positive breast cancer, but in most cases, resistance to the treatment develops within several years. The prognosis for HER2-positive breast cancer patients is worse than for those with other subtypes of the illness.
When they treated mice modeling HER2-positive breast cancer with a PTP1B inhibitor called MSI-1436 (also called trodusquemine), Tonks and colleagues inhibited signaling by HER2 proteins.
The new paper by Tonks and collaborators importantly reveals an alternative binding site, called an allosteric site, that does not present the biochemical difficulties that the active, or "catalytic," binding site does. This allosteric site is a target of the candidate drug trodusquemine.
The paper has been published online in the journal Nature Chemical Biology.