Mechanisms of Resistance to Androgen Deprivation Therapy in Advanced Castration-Resistant Prostate Cancer (CRPC)

Abstract

The overall hypothesis is that expression of the dipeptidase DPP4 is downregulated in prostate cancer (PCa) as a mechanism of resistance to androgen deprivation therapy (ADT). My overall objective is to demonstrate that DPP4 downregulation is a mechanism of ADT-resistance and PCa progression and to identify the specific pro-survival growth factor/cytokine targeted by DPP4 for degradation and its associated signaling cascade. Aim 1 will assess the effect of DPP4 downregulation and overexpression on the sensitivity of PCa xenografts to castration. Aim 2 will identify the pro-survival growth factor/cytokine targeted by DPP4 for degradation and the downstream signaling cascades effected. Aim 3 will extend the significance of DPP4 downregulation into primary PCa and CRPC clinical specimens and assess the interaction of DPP4 inhibition with ADT.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2019
Accession Number
AD1086511

Entities

People

  • Joshua W. Russo

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cells
  • Computational Biology
  • Data Sets
  • Department Of Defense
  • Electronic Mail
  • Gene Expression
  • Growth Factors
  • Health Services
  • Materials
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Statistical Analysis

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  • Prostate Cancer Biology.