Targeting cancer evolution offers a way to foil drug resistance

Solutions to cancer drug resistance could come from new understanding about tumor evolution and advances in liquid biopsies.

A growing crop of researchers and companies are tackling cancer drug resistance by preempting tumors’ tendencies to adapt, rather than responding to resistance after it develops. Though still in their infancy, these therapies could get a lift from up-and-coming liquid biopsy technologies that can catch tumors early and monitor their evolution.

Oncologists typically fight drug resistance through sequential treatment with different lines of therapy. Molecularly targeted drugs and diagnostics for resistance mutations have made the process more rational, but treatment strategies remain overwhelmingly reactive.

“It’s the equivalent of playing whack-a-mole, which can work for a while, but is kind of a losing game,” said James DeGregori, a professor of biochemistry and molecular genetics, molecular biology and immunology at University of Colorado Anschutz Medical Campus.

The limits of the reactive approach were made clearer by sequencing data accumulated through the TRAcking Cancer Evolution through therapy (Rx) (TRACERx) trials led by Charles Swanton, chief clinician at Cancer Research UK and a group leader at the Francis Crick Institute.

“The amount of diversity in the tumor is simply immense,” said Swanton. “There’ll always be one or more cells in the tumor that are resistant to the therapy you’re using, just by chance alone.”

He and other researchers are aiming to

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