UT Health San Antonio seeks to partner with a diagnostic products company to develop and commercialize a clinical diagnostic with the potential to determine if a patient with estrogen receptor (ER) positive breast cancer is suitable for treatment with endocrine therapy (e.g., tamoxifen and/or the aromatase inhibitors anastrozole (Arimidex®), letrozole (Femara®), and others).
Background:
Overall, approximately 60-65% of breast cancers are found to be ER-positive upon biopsy. Estrogen is a growth hormone and in patients with ER+ breast cancers, estrogen binds to the estrogen receptors in the patient's breast cancer cells and can be thought of as the "fuel" that drives the breast cancer cells. ER+ breast cancer patients frequently receive endocrine therapy with the goal of eliminating the mitogenic effects of estrogen. Unfortunately, many cancers eventually select for tumor cells that can survive despite the absence of estrogen. These estrogen-insensitive tumors frequently metastasize and are associated with very poor prognosis. Recent treatment approaches for hormone-insensitive breast cancers include use of the Signal Transduction Inhibitors (STIs) given with the goal of inhibiting EGFR/HER2 receptor signaling. However, this approach has not proven particularly effective in combating endocrine resistance, suggesting the involvement of a novel cell survival pathway. DBC1, a protein involved in many areas of cancer, may be responsible for mediating this novel prosurvival pathway and thus may be an important therapeutic target.
DBC1 is upregulated and complexed with ER2 in hormone independent tumor cells. Drs. Boyer and Trauernicht have discovered that inhibiting the formation of the DBC-1/ER2 complex by siRNA-mediated depletion of cellular DBC-1 results in rapid apoptosis. This suggests the complex is at least partially responsible for cancer cell survival in ER+ hormone independent breast cancer cells and that disrupting the formation of the DBC-1/ER2 complex by siRNA or other means may result in a meaningful improvement in clinical outcomes.
Commercial Applications & Advantages:
This invention is applicable to patients with ER+ hormone independent breast cancers for treatment (chemo/radiation adjuvant for treatment refractory cancers) and prevention (used in conjunction with standard of care estrogen ablation therapies, prevent the progression of hormone sensitive tumors into hormone-independent breast cancers).
Additionally, the invention provides the benefits over the current standard of care listed below:
- Addresses a great unmet need: another treatment option for patients with advanced ER+ breast cancer
- Potentially improve overall survival by stopping development of treatment-resistant breast cancers,
- Decrease overall healthcare system costs associated with the emergence of treatment resistant cancers