The story

This is the work of one group over two decades at SUNY Downstate Medical Center in Brooklyn: Matthew Pincus, Josef Michl, Ehsan Sarafraz-Yazdi and colleagues, later with surgeons at Drexel and Thomas Jefferson. Their starting point was the p53 to MDM-2 interaction, the most studied handshake in cancer biology, and their twist was to notice it could be attacked where the protein sits in the membrane rather than in the nucleus. In 2006 they showed the sibling peptide PNC-28 destroying pancreatic tumours implanted in mice when given into the abdominal cavity over two weeks, with no effect on normal pancreatic or breast cells. In 2010 they showed the whole intact peptide, rather than any fragment, was what lysed the cells, and worked out the binding shape. In 2014 and 2020 they took it to leukaemia, where it killed leukaemia cells but spared normal blood-forming cells, and to ovarian cancer cells taken fresh from patients, including cells from tumours that had become resistant to chemotherapy. In 2022 came the electron microscopy pictures of the pores themselves, and in 2024 the finding that mitochondrial membranes are hit as well. The same year Pincus set out the general idea under the name poptosis: killing a cell by making a hole in it rather than by persuading it to kill itself.