Ire1-α Inhibitors to Treat Invasive Estrogen-Receptor Positive Breast Cancers
Categories: “Cancer Therapeutics“
Reference #: 2011-014
Resistance to endocrine therapies remains a significant clinical problem in the treatment of advanced Estrogen Resistant positive (ER+) breast cancers. Georgetown researchers found that X-Box Protein 1 (XBP1) splicing is a key factor in inducing resistance to endocrine therapy and that such splicing is induced by endonuclease, Inositol-Requiring Enzyme 1 alpha (IRE1α). The present invention describes small molecule IRE1α inhibitors that block XBP 1 splicing. In addition to creating new therapies, the present invention also provides a unique opportunity to further understand the mechanism of endocrine resistance.
* Potential therapeutics for the treatment of endocrine-resistant breast cancers, metastatic breast cancers and other types of cancer.
* A novel targeted therapy
* Potential to improve outcomes for the majority of the breast cancer patients
* Advantageous over endocrine therapy for ER+ cancers
Stage of Development
Researchers have demonstrated blocking XBP1 splicing inhibits cell proliferation in estrogen-receptor positive breast cancers cells in a dose-dependent manner. Studies are ongoing in vivo.
Manuscript in preparation
Sivanesan Dakshanamurthy, Ayesha N. Shahjahan, Robert Clarke, and Milton L. Brown