Molecular Characterization of Androgen Independence to Delay Progression to Hormone Refractory Prostate Cancer
Abstract
Progression to hormone-refractory prostate cancer (HRPC) remains a major obstacle to effective control of metastatic disease. The overall goal of this project is to define cellular and molecular markers for the progression of androgen dependent (AD) to androgen independent (AI) and to develop more effective androgen deprivation-based treatment schedules capable of delaying prostate cancer (CaP) tumor progression from locally advanced to widely metastatic disease. In the past year, primary efforts were focused on the following tasks: 1) Establishment of an in vitro assay to demonstrate the cross-talk between androgen dependent LNCaP and the androgen independent CL1 progeny; The cross-talk between AD LNCaP and Al CL1 was also investigated in vivo in SCID mice; 2) Validation of the Flap structure-specific endonuclease (FEN-1), one of the molecular markers identified through the LNCaP/CL1 model, as a CaP prognosis marker on large-scale human CaP tissue microarrays. 3) Delineation of the lineage relationship between LNCaP and CL1 based on characterization of cell surface CD markers. In summary of all the results obtained in the funding period, the current DOD grant has allowed us to understand the molecular and cellular changes during progression from AD to AI cancer, which provides clinically useful biomarkers for Cap prognosis. Studies of intermittent androgen depletion and chemotherapy agents that induce apoptosis to AU cancer open doors for novel therapies targeting Al Cap.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437680
Entities
People
- Arie S. Belldegrun
Organizations
- University of California, Los Angeles