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