Rachel Schiff, PhD

Identifying drivers of resistance and new treatment strategies in advanced estrogen receptor-positive and HER2-positive breast cancers.

Impact

While treatments for estrogen receptor (ER)-positive and HER2-positive breast cancers have greatly improved outcomes for patients, many still experience disease progression when their cancers develop resistance. These resistant cancers can spread, leading to worse outcomes and limited treatment options. By identifying how resistance develops, researchers can design more effective treatments that prevent recurrence and improve survival. Drs. Osborne and Schiff and their teams conduct laboratory and clinical studies to understand resistance to endocrine and anti-HER2 therapy and develop new treatment strategies to overcome it. They have a growing panel of sophisticated experimental models of drug resistance and metastasis, as well as data from clinical specimens—valuable resources to advance the understanding of the molecular drivers of drug resistance that can be shared with the wider research community.

Progress Thus Far

In the past several years, the research group has used their growing panel of diverse and clinically relevant models to reveal several mechanisms of resistance to ER- and HER2-targeted therapies. In HER2-positive breast cancer, resistance often occurs through reactivation of HER pathways or alternative signaling, but combinations of HER2 targeting drugs and inhibitors of growth factors can restore sensitivity. Importantly, their work has also revealed ways to enhance the effectiveness of promising drugs like tucatinib (Tukysa®) and trastuzumab deruxtecan (Enhertu®).

What’s next

In the coming year, the lab will deepen its studies on specific pathways and proteins to better understand how they drive resistance. They plan to test new treatment combinations, and they will also develop additional drug-resistant models of brain metastasis and HER2-low cancers to uncover new therapeutic vulnerabilities. Lastly, they will evaluate personalized immunotherapeutic strategies to tackle drug-resistant disease and improve patient outcomes.