Many proteins implicated in cancer growth and survival are extremely difficult to target directly with drugs, but scientists at Genentech, a Roche subsidiary, have found a roundabout therapeutic strategy for limiting the activity of these otherwise intractable proteins.
Reporting in Nature, a Genentech-led team has identified two small molecule inhibitors of ubiquitin-specific protease-7 (USP7), an enzyme that strips other proteins of small tags that mark them for destruction by the cell’s garbage disposal system.
These drugs, by blocking USP7 near its active site, set off a molecular chain reaction that helps stabilize a master tumour suppressor protein called p53, an elusive “undruggable” target. In lab experiments, the molecules killed cancer cells in a dish and augmented the anti-tumour effects of other chemotherapeutic agents.
The compounds lack certain properties required for human use, and so further drug development efforts are still needed to build on the finding of this anti-USP7 strategy.