ABI1 Regulates Transcriptional Activity of Androgen Receptor by Novel DNA and AR Binding Mechanism

Background:

The gene Abelson interactor protein-1 (ABI1) encodes a member of the Abelson-interactor family of adaptor proteins. These proteins facilitate signal transduction as components of several multiprotein complexes, and regulate actin polymerization and cytoskeletal remodeling through interactions with Abelson tyrosine kinases. The androgen receptor (AR) protein functions as a steroid-hormone activated transcription factor. ABI1 and AR are widely expressed in human tissues. Many cancers show sex-specific tumorigenesis, tumor progression, and sensitivity to hormonal drugs. The ABI1-AR axis might play critical roles in these tissue and drug sensitivities and toxicities. For example, ABI1 regulates a specific subset of genes associated with prostate tumor progression. These genes are biomarkers and potential targets of tumor progression.

Technology Overview:

This technology defines ABI1-AR reciprocal regulation involving two non-exclusive molecular mechanisms of ABI1-AR and ABI1-DNA interactions. ABI1-DNA binding activity predicts survival of prostate cancer patients. ABI1 binds AR via a multivalent interaction. The ABI1-AR transcriptional program is altered during tumor progression and by anti-androgen treatments, suggesting that ABI1 is a key plasticity regulator in PCa by coupling its actin regulatory and signaling functions to transcriptional regulation. ABI1-AR reciprocal regulation has far reaching implications for tumor plasticity and androgen-sensitive pathogenesis. These interactions are co-regulated during PCa evolution and clinical treatment promoting tumor plasticity and progression. This provides new paths for biomarker and drug design discovery in PCa.

Advantages:

•    Provides a novel mechanism for predicting survival rates among cancer patients.
•    May enable drug discovery for a wide variety of cancers.

Applications:

The primary applications for this technology are the development of biomarkers for assessing cancer patient survival rates, and drug discovery.

Intellectual Property Summary:

US Provisional Patent Application Ser. No. 63/463,457, filed May 2, 2023. 

Stage of Development:

TRL 3 - Experimental proof of concept

Licensing Status:

This technology is available for licensing.

Licensing Potential:

This technology would be of interest to anyone involved in the development of biomarkers and/or therapeutics for cancer, including:
•    Pharmaceutical companies.
•    Hospitals.
•    Medical research laboratories.
•    Universities.