For five decades, scientists have known about a notorious cancer-causing enzyme called SRC. But they always assumed it only appeared on the inside of cells, where it sent signals that fueled tumor growth and stayed hidden from the immune system.

But now researchers at UC San Francisco have discovered that the SRC enzyme also appears like a flag on the surface of bladder, colorectal, breast, pancreatic, and probably many other tumor cells.

As cancer cells furiously divide, they produce a lot of garbage. In healthy cells, the trash gets broken down. But in tumors, the recycling system gets overwhelmed, and the cells expel some of their trash. This pushes the SRC enzyme onto the surface of the cell, where it is visible to potential therapies, like antibodies.

“No one thought to look for it on the outside, said Jim Wells, PhD, professor of Pharmaceutical Chemistry at UCSF and senior author of the paper, which appears in Science on March 12. “Our discovery enables us to test proven immunotherapies on this new tumor target.”

Researchers targeted the SRC enzyme with antibodies that carried radioactive payloads or summoned immune cells. This killed the cancer cells, shrinking tumors in mice. The new target could apply to up to half of all tumors.

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