Ire1-α Inhibitors to Treat Invasive Estrogen-Receptor Positive Breast Cancers

Categories:  “Cancer Therapeutics

Reference #: 2011-014

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)


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.

Relevant Publications

Manuscript in preparation


Sivanesan Dakshanamurthy, Ayesha N. Shahjahan, Robert Clarke, and Milton L. Brown