An international phase III clinical trial found that metastatic colorectal cancer patients with a rare genetic tumor mutation called KRAS G12C experienced superior progression-free survival rates compared to standard of care when offered a combination treatment of KRAS inhibitor sotorasib and monoclonal antibody panitumumab.
When I first proposed targeting PCNA (proliferating cell nuclear antigen) as a therapeutic approach, the response I got was: “No one will ever make a drug against PCNA. It’s undruggable.” The protein lacks enzymatic activity, has a disordered region, and binds to over 200 other proteins within the cell. From a traditional drug development perspective, these characteristics made PCNA an impossible target.
