Seth Wander MD, PhD, discusses research presented at the 2022 San Antonio Breast Cancer Symposium, focusing on the genomic and molecular mechanisms of resistance to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

Dr Wander highlights projects being done at Mass General in this field and explains this research could lead to personalized, biomarker-based approaches for determining how individual patients will respond to CDK4/6 inhibitors.

Transcript:

Hi, my name is Seth Wander. I'm a medical oncologist at Massachusetts General Hospital in Boston. Our research interests have been primarily focused on genomic and molecular mechanisms of resistance to cyclin-dependent kinase inhibitors and antiestrogens in metastatic breast cancer. We're excited to be here at San Antonio Breast Cancer Symposium in Texas to discuss a lot of new advancements in this area.

Over the last several years, our work and other's have demonstrated that the landscape of resistance to these drugs is quite heterogeneous. There are a variety of different drivers that can impact multiple different cellular pathways, including cell cycle regulators, as well as oncogenic signal transduction pathways. We'll present some data here at SABCS, demonstrating some preliminary findings regarding NF1, based on a single-institutional, retrospective experience at Mass General Hospital. These results suggest that perhaps NF1 mutations may provoke CDK inhibitor resistance, and we think this may be through the RAS pathway, which was previously implicated by prior work.

We're going to be spending some time over the next few months and year trying to expand upon that effort, both in clinical samples, as well as in the laboratory. And over the course of the meeting, we're excited to be discussing a variety of other new abstracts, based upon developing new biomarkers for response and resistance in large patient populations that have received CDK4/6 inhibitors.

We're hopeful that, based on this work and other work coming out in the coming months and years, that we might be able to develop personalized biomarker based approaches, to determine who might do better or who might do worse with CDK4/6 inhibitors at various stages of treatment.