Dartmouth team tags HER4 as a key culprit for HER2 drug resistance

In recent years, cancer drug researchers have developed some major new drugs for treating HER2-positive breast cancer. But patients taking these targeted new drugs like Herceptin (trastuzumab) and Tykerb (lapatinib) still develop resistance to them. Now a team at Dartmouth says it has identified a key pathway for resistance that points to a new class of third-line therapies.

Using lapatinib-resistant tumors in mice, the team says they nailed down clear evidence that HER4, or ERBB4, is a key driver of HER2-positive cancer cases that have become resistant to therapy. And while the topic has been a controversial one, the investigators say they're confident in their conclusions.

Dartmouth's Manabu Kurokawa

"We have shown that when ERBB2-positive breast cancers develop resistance to anti-ERBB2 drugs, they shift their dependence from ERBB2 to ERBB4, which acts as a new driver of cancer survival and proliferation," explained Manabu Kurokawa at Dartmouth's Norris Cotton Cancer Center.

Kurokawa's hunch is that the PI3K/AKT pathway is the key mechanism needed for the shift toward resistance, adding that HER4 drugs would appear to be likely candidates for second- and third-line treatments for drug-resistant patients. And now the team plans to do more work to see if they can verify their work, which is being funded by a grant from the NIH.

- here's the release

Suggested Articles

German scientists are targeting a protein-cutting enzyme that many viruses, including the coronavirus COVID-19, need to replicate.

UPenn scientists found blocking the Wnt/beta-catenin pathway in endothelial cells made chemotherapy more effective in mouse models of glioblastoma.

Astellas’ Xospata and Novartis’ Rydapt may help treat lung cancer that has grown resistant to EGFR inhibitors, researchers discovered.