Inhibition of RAR/RXR signaling for adenoid cystic carcinoma treatment
This technology is an approach to treating adenocarcinomas that targets retinoic acid receptor/retinoid X receptor signaling to either block myoepithelial-to-ductal differentiation or selectively reduce the viability of ductal-like tumor cells.
Unmet Need: Lack of effective, systemic, targeted therapies for adenocarcinoma
Adenoid cystic carcinoma (ACC) is a lethal and aggressive malignancy of the secretory glands, characterized by local invasion, perineural spread, and frequent distant metastasis. There are currently no approved medical treatments, and the standard of care relies primarily on surgical resection of primary tumors, sometimes followed by radiation therapy to prevent local recurrence. While these approaches can control localized disease, they are often insufficient for recurrent, unresectable, or metastatic cases, do not address the underlying molecular drivers of the disease, and cause significant morbidity, particularly in the craniofacial region. Thus, there is a critical need for effective systemic, targeted therapies that can extend survival, improve long-term disease control, and reduce treatment-related harm.
The Technology: Modulation of RAR/RXR signaling to systemically target aggressive adenoid cystic carcinoma (ACC) cells
This technology is a strategy for treating adenocarcinomas that targets aggressive adenoid cystic carcinoma (ACC) by modulating retinoic acid receptor/retinoid X receptor (RAR/RXR) signaling. The approach first identifies specific ACC cell populations using surface markers, distinguishing more aggressive myoepithelial-like cells from ductal-like cells. It can then modulate tumor composition by using RAR/RXR agonists to drive the myoepithelial-like cells toward a ductal-like state. Once cells have adopted a ductal-like phenotype, they become vulnerable to RAR/RXR inverse agonists, which selectively kill them.
This technology has been validated in patient-derived xenografts of human AACs and in vivo models.
Applications:
- Treatment for adenoid cystic carcinoma and other retinoid-dependent cancers
- Adjuvant therapy in combination with radiation or chemotherapy
- Research tool to study RAR/RXR signaling and tumor differentiation
- Tool for diagnostic stratification of ACC based on cellular composition
- Platform to investigate tumor plasticity and differentiation dynamics
Advantages:
- Selectively targets aggressive tumor cells
- Dual-action therapeutic approach
- Systemic, non-invasive therapy
- Reduces tumor heterogeneity
- Addresses underlying drivers of disease
- Targeted therapy
Lead Inventor:
Piero D. Dalerba, M.D.
Patent Information:
Patent Pending (US20260034081)
Related Publications:
Tech Ventures Reference:
IR CU23276
Licensing Contact: Kristin Neuman