Development of km23-Based Diagnostics and Therapeutics

Abstract

Similar to other solid tumors, ovarian cancers are resistant to the growth inhibitory effects of the natural epithelial growth inhibitor TGF beta, suggesting that alterations in TGF beta pathways contribute to ovarian cancer progression. The TGF beta resistance is frequent, perhaps exceeding 75% of cases, especially for recurrent ovarian cancers. Despite the high frequency of TGF beta resistance that occurs in ovarian cancers, thus far, no clinically useful agents, which target the signaling pathways of any of the TGF beta superfamily members, have been developed for this disease. Accordingly, there is a great need to develop TGF beta-based agents and indicators for the diagnosis, therapy, and prognosis of ovarian cancer. Further, TGF beta and some of its signaling components can function as tumor suppressors. We have identified a novel TGF beta signaling component (km23) that is altered in 42% of ovarian cancer patient tumors. km23 mediates growth inhibition and other TGF beta responses. A deletion mutant in the Drosophila homologue of km23, similar to the truncation of km23 we identified in ovarian cancer patient samples, resulted in an increase in mitotic index, suggesting that km23 may function as a tumor suppressor. We are in the process of developing anti-cancer diagnostics and therapeutics using km23 as the target.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA425801

Entities

People

  • Kathleen M. Mulder

Organizations

  • Pennsylvania State University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Cancer
  • Carcinoma
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoskeleton
  • Epithelial Cells
  • Gene Expression
  • Genetics
  • Growth Factors
  • Health Services
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Proteins
  • Therapy

Fields of Study

  • Medicine

Readers

  • Atmospheric Science/Meteorology
  • Molecular Biology and Genetics
  • Oncology (Cancer Research).