Characterizing and Targeting Androgen Receptor Pathway-Independent Prostate Cancer
Abstract
In this proposal, we aim to test the hypothesis that complete AR pathway inhibition selects for subpopulations of tumor cells that are completely independent of AR signaling and further, that these resistant cells will have activated---and be dependent upon---a limited set of specific survival and growth regulatory pathways (stemming from genomic alterations in specific oncogene networks) that can be identified and targeted. The proposal comprises three Specific Aims: Aim 1 will define the genomic alterations and transcript variants that comprise states of ARIPC. Aim 2 will determine if targeting/inhibiting the survival pathway(s) that emerge following AR pathway ablation will restrain tumor growth. Aim 3 will determine if simultaneously co-targeting the AR pathway and ARIPC survival pathway(s) in ARsensitive prostate cancers will augment tumor responses and delay/prevent recurrences. During this funding period we have: (i) completed laser capture microdissection of CRPC prostate cancers to acquire RNA and DNA; (ii) completed transcript profiling for 196 CRPC metastasis; (iii) completed genomic analyses for 196 prostate cancer metastasis; (iv) identified a program of AR-repressed genes that may influence the development of CRPC; (v) completed preclinical studies of two putative AR-bypass pathways. Initiated integrated molecular analyses and high-throughput gene knockdown screens of advanced metastatic CPRC to identify additional molecular pathways that operate to promote prostate cancer growth in the absence of AR signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2012
- Accession Number
- ADA574344
Entities
People
- Peter S Nelson
Organizations
- Fred Hutchinson Cancer Center