Grant: Project Grant

Breast cancer is the most prevalent form of cancer among women (excluding non-melanoma skin cancers), representing 25% of all new cancer cases in women in 2022. Fulvestrant, a well-tolerated hormonal agent, is the foundation of treatment for most breast cancers, but resistance to this treatment eventually develops. Because traditional drugs cannot directly address the causes of this resistance, we propose to target them with biologics, and specifically small interfering RNA (siRNA). For greater success, we propose to incorporate these biologics into lipid nanoparticles (i.e., nanobeads similar to the ones used to deliver the mRNA vaccines) yet with a key difference. The lipid nanoparticles will include our newly re-designed fulvestrant and siRNA to enhance delivery to the inside of the cell and thereby achieve greater success against chemoresistant breast cancer. There are several key innovations: synthesis of novel, re-designed fulvestrant analogues (which maintain the potency of fulvestrant itself), formulation of these re-designed fulvestrant analogues into lipid nanoparticles, and their co-delivery with siRNA against an undruggable target. By bringing together world leading experts in breast cancer, colloidal drug aggregate formulation, lipid nanoparticles, and siRNA delivery, we are poised for success in designing better treatment strategies for women with estrogen receptor positive breast cancer.