"Phase  clinical trial data published this week in the journal Clinical Cancer Research show early promise of the investigational anticancer agent tucatinib formerly ONT against HER breast cancer. The  women treated had progressed despite a median  previous treatment regimens. Twentyseven percent of these heavily pretreated patients saw clinical benefit from the drug with at least stable disease at  or more weeks after the start of treatment. These data led to two subsequent Phase Ib studies resulting in tucatinib earning FDA fasttrack status and the expansion of this study once meant only to demonstrate drug safety into the pivotal trial that will determine approval. Usually we expect the results of a phase  clinical trial to give us data that we can use to guide the results of future treatments. This is a great case in which for many of these patients the results were immediate. There are women who are alive today because of this drug says Virginia Borges MD MMSc director of the Breast Cancer Research Program and Young Womens Breast Cancer Translational Program at the University of Colorado Cancer Center. Borges has been a major driver of the drugs development from its invention at Array Biopharm in Boulder CO and now through clinical trials of the drug which is licensed to Cascadian Therapeutics of Seattle WA.  Tucatinib is a small molecule inhibitor of the HER growth factor receptor. The drug works by targeting the HER tyrosine kinase  a link in the chain of communication that allows HER receptors to signal the growth of the cell. The fact that it is a small molecule means the drug is able to pass through the bloodbrain barrier to act against brain metastases of the disease. HER breast cancer is more likely to affect younger women and also more likely than other breast cancers to metastasize specifically to the brain. Working with Borgess Young Womens Breast Cancer Translational Program at CU Cancer Center young investigator Elena Shagisultanova MD PhD recently earned a .m competitive ASPIRE grant from Pfizer Inc. to conduct a clinical trial exploring the use of tucatinib against socalled triple positive breast cancer  those cancers driven by both estrogen and progesterone receptors and the HERneu oncogene.  When both estrogen and HER are positive they counteract the therapy aimed at one or the other playing off each other like kids splitting parents Borges says. More specifically when both avenues are present the crosstalk leads to tumors being resistant to treatment as either avenue can allow the cancer to survive therapy. Previous trials concurrently targeting estrogen and HER have been according to Borges lackluster resulting in no changes to the standard of care. The forthcoming trial lead by Shagisultanova will be a multicenter clinical trial with CU Cancer Center as the lead site testing the combination of three drugs  tucatinib plus the antiestrogen receptor drug letrozole and the cell cycle inhibitor palbociclib  against breast cancers positive for both HER and estrogen receptors.  Tucatinib could be a substantially practicechanging drug Borges says meaning that in addition to the drugs current investigations as a third fourth or morethanfifthline treatment she envisions its use sooner in the arc of breast cancer treatment and with far more patients. I think this drug has an extremely high likelihood of being approved for women with HER breast cancer for use after previous treatments Borges says. And its going to be an especially important drug due to its ability to control brain metastases. The opportunity to study it as a frontline drug for recurrent triple positive breast cancer could even someday help us prevent or delay these brain metastases. Because the drug is taken in pill form and has a very favorable side effect profile Borges points out that it is relatively patientfriendly allowing women to avoid treatments in infusion centers and also many of the sideeffects associated with chemotherapies.  Ongoing updates are expected in journals and meetings later in ."