A lab-designed drug targets a common cancer driver while sparing normal cells, Weill Cornell finds

Researchers at Weill Cornell Medicine have found a way to hit a common cancer driver that may spare healthy cells, the Cornell Chronicle reported on 2 November. In lab tests, a compound they designed slowed the growth of cancer cells with a specific genetic loss while leaving normal cells alone. The study is published in Nature Chemical Biology.

The WNT pathway, a stubborn target

The WNT signaling pathway is overactive in almost all colorectal cancers, more than half of breast cancers and substantial shares of liver, lung, prostate, skin, bone and gynecologic cancers. Drugs that block it have been hard to develop. Earlier inhibitors of tankyrase, a pair of enzymes that support WNT signaling, hit both enzymes and caused dose-limiting side effects in early clinical trials.

“Targeting the WNT pathway in cancer without side effects has been a challenge for decades now.” — Lukas Dow, Weill Cornell Medicine

Using the tumor’s own missing gene

Most cancers lose stretches of DNA, and a common loss removes the TNKS1 gene. Those cells then depend on its twin, TNKS2. The team first confirmed the idea by switching TNKS2 off genetically, then designed a compound that inhibits TNKS2 about 30 times more strongly than TNKS1. In lab dishes, it suppressed the growth of cancer cells with partial or full loss of TNKS1 and had no apparent effect on cells with normal TNKS1. “We stumbled across this by accident,” Dow said.

What it means for patients now

This is early preclinical work: the results come from cells in lab dishes, and no animal data were reported. The compound is not a medicine, and patients cannot receive it. The Dow lab is now developing a next-generation compound with better drug-like properties, and if it performs well in full preclinical tests, the researchers hope to move it into clinical trials. “There's still a lot of work to be done,” the article notes.

The research was led by Lukas Dow, professor of biochemistry in medicine at the Sandra and Edward Meyer Cancer Center, with first author Jill Zimmerman, and funded in part by the National Cancer Institute. More stories on cancer research are collected under cancer treatment.