The Ubiquitin System in Cancer

Last May, the US Food and Drug Administration approved the first weapon in what could become a brand new arsenal against cancer. That weapon is Velcade (bortezomib), a drug that inhibits an intracellular protein-disposal system known as ubiquitin-mediated proteolysis (UMP). Made by Cambridge, Mass.-based Millennium Pharmaceuticals, Velcade improves and prolongs the lives of some patients with relapsed and refractory multiple myeloma. As a succession of companies tested Velcade (also called P

Douglas Steinberg
Sep 21, 2003

Last May, the US Food and Drug Administration approved the first weapon in what could become a brand new arsenal against cancer. That weapon is Velcade (bortezomib), a drug that inhibits an intracellular protein-disposal system known as ubiquitin-mediated proteolysis (UMP). Made by Cambridge, Mass.-based Millennium Pharmaceuticals, Velcade improves and prolongs the lives of some patients with relapsed and refractory multiple myeloma.

As a succession of companies tested Velcade (also called PS-341) over the past eight years, this boronic acid compound aroused skepticism and puzzlement. Besides oncogenic proteins, "there are numerous other proteins whose degradation is controlled by the [UMP] pathway," says I. Bernard Weinstein, professor of medicine at Columbia University. "So it's not intuitively obvious that this would be a mechanism that you'd want to target."

Julian Adams, head of the team that discovered Velcade, confesses: "I wasn't surprised it had an effect on cancer. My surprise--and what took me...