A third long standing area of interest in our laboratory is the development of improved therapeutic strategies to target the ERa in breast cancer. Our past effort has led to the discovery that the proteasome inhibitor Bortezomib can enhance the efficacy of the anti-estrogen receptor drug fulvestrant. This work has led to a large phase II randomized clinical trial in post-menopausal women with metastatic breast cancer. The results of this trial revealed the superiority of the fulvestrant-bortezomib combination over the fulvestrant alone and suggests that the combination delays acquired resistance to fulvestrant.

We currently are initiating a pre-operative clinical trial in premenopausal women to compare the efficacy of tamoxifen and fulvestrant based on data obtained in our laboratory suggesting that cyclin D1 can act as a biomarker to better orient the use of these drugs. Our data suggests that the cdk-dependent and independent roles of cyclin D1 in the regulation of the ERa are critical in targeting these drugs in the clinic.

In the future, our goal is to design clinical trials specifically against pregnancy-associated breast cancers. We are also working toward the goal of targeting the UPR^mt for therapy.