Drug Development for Prostate Cancer and other Metastatic Processes

Our understanding of the biology of CRPC progression has led to the discovery of more effective targeted approaches that involve modulation of the androgen-AR system. We are interested in the preclinical and clinical development of novel therapeutics with efforts on characterizing their molecular and clinical pharmacology as well as evaluating for potential biomarkers of treatment response and resistance. We are currently developing novel targeted therapies against metastatic CRPC. We have embarked upon a new drug screening project to identify novel drug targets and develop rationale combination therapies using next-generation sequencing and a matrix combination screening platform that is designed to identify novel drug targets/pathways for CRPC. We are currently testing promising combinations in various preclinical prostate cancer models with the goal of selecting the best treatment combination to move towards clinical development. As we move into the era of precision medicine, the growing relevance of genetic alterations to prostate cancer (PCa) development and treatment demonstrates the importance of characterizing preclinical models at the genomic level. Our study investigated the genomic characterization of eight PCa cell lines to understand which models are clinically relevant. We designed a custom AmpliSeq DNA gene panel that encompassed key molecular pathways targeting AR signaling, apoptosis, DNA damage repair, and PI3K/AKT/PTEN, in addition to tumor suppressor genes. We examined the relationship between cell line genomic alterations and therapeutic response. In addition, using DepMap's Celligner tool, we identified which preclinical models are most representative of specific prostate cancer patient populations on cBioPortal. These data will help investigators understand the genetic differences in preclinical models of PCa and determine which ones are relevant for use in their translational research.