In an effort to expand the number of cancer gene mutations that can be specifically targeted with personalized therapies, researchers at University of California San Diego School of Medicine and Moores Cancer Center looked for combinations of mutated genes and drugs that together kill cancer cells. Such combinations are expected to kill cancer cells, which have mutations, but not healthy cells, which do not. The study, published July 21 in Molecular Cell, uncovered 172 new combinations that could form the basis for future cancer therapies.

“Oncologists here at Moores Cancer Center at UC San Diego Health and elsewhere can often personalize cancer therapy based on an individual patient’s unique cancer mutations,” said senior author Trey Ideker, PhD, professor of genetics and bioengineering at UC San Diego School of Medicine and Jacobs School of Engineering. “But the vast majority of mutations are not actionable — that is, knowing a patient has a particular mutation doesn’t mean there’s an available therapy that targets it. The goal of this study was to expand the number of mutations we can pair with a precision therapy.”

Most cancers have gene mutations that do one of two things — promote cell growth or prevent cell death. The first type is the target of many therapies, which inhibit cell growth. But it’s much harder to develop therapies that restore malfunctioning genes that should be triggering cell death in abnormal cells, known as tumor-suppressor genes.

Rather than target a tumor-suppressor gene directly, Ideker and team took the approach of identifying genetic interactions between a tumor suppressor gene and another gene, such that simultaneous disruption of both genes selectively kills cancer cells.