The Role of NF-kappaB in Promotion and Survival of Androgen-Dependent and Independent Prostate Cancer

Abstract

Androgen ablation remains the only effective form of systemic therapy for patients with advanced prostate cancer due to the ineffectiveness of standard forms of cancer therapy. The transcription factor NF-kappaB has emerged as a key regulator of oncogenesis based on its ability to promote cell proliferation, suppress apoptosis, and to promote metastasis and angiogenesis. Additionally, NF-kappaB has been shown to be activated by cancer therapies such as radiation and chemotherapy to suppress therapy-induced apoptosis. The underlying hypothesis of this proposal is that constitutive activity of NF-kappaB in androgen-dependent prostate cancer provided either a growth or survival function and that enhanced activation of NF-kappaB, potentially through p65/RelA phosphorylation, promotes recurrence% of the androgen-independent phenotype. It also proposed that NF-kappaB activation provides a strong level of prostate cancer chemoresistance. The aims (modified following funding reduction) were to: (1) characterize therapeutic approaches for the inhibition of andogen-dependent and androgen-independent CWR22 tumor growth and (2) determine whether combination treatment of chemotherapy and NF-kappaB inhibitors will provide a new therapeutic approach for prostate cancer treatment.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA430433

Entities

People

  • Albert S Baldwin

Organizations

  • University of North Carolina at Chapel Hill

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Angiogenesis
  • Apoptosis
  • Biomedical Research
  • Cancer
  • Chemotherapy
  • Inhibition
  • Inhibitors
  • Metastasis
  • Neoplasms
  • North Carolina
  • Prostate
  • Prostate Cancer
  • Survival
  • Therapy
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).
  • Prostate Cancer Biology.