Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

During the grant period, we have achieved the following: 1) Identified two regions in the AR ligand binding domain (LBD) that confer the microtubule binding activity; 2) Characterized the functional significance of the AR-microtubule interaction and provided compelling evidence to suggest that the intracellular localization and activity of AR microtubules is regulated by its association with the microtubules; 3) Provided a fundamental understanding of the constitutive activities of LBD-truncated AR splice variants, such as AR-V7 and ARv567es; 4) Developed and validated a whole-blood based assay for the detection of AR-V7 and ARv567es, and 5) Identified a profound interaction of AR LBD hotspot mutations.