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Function and Clinical Utility of the HOXB13 Cofactors MEIS1 and MEIS2 in Prostate Cancer Progression

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[Technical Report, Annual Report]

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Prostate cancer continues to be a significant and incurable health problem that will only become more prevalent as life expectancy increases. Thus, there is a dire need for alternative approaches to prevent cancer initiation, discern indolent from aggressive tumors, and treat metastatic disease. Recent evidence of germline HOXB13 mutations within a subset of familial prostate cancers supports a key role for HOX regulation pathways in prostate initiation and progression. Moreover, the majority ofHOXB13 mutations are located within the MEIS-interacting domain and thus emphasizes the importance of MEIS-HOX protein interactions in prostate tumor biology. This proposal builds upon significant published and unpublished work demonstrating a key role for the MEIS proteins as critical transcription factors and HOX protein co-factors in suppressing prostate tumor progression, blocking cell proliferation, and promoting anti-metastatic gene expression. However, there remain significant shortcomings in our ability to translate our pathologic and mechanistic discoveries into patient benefit. The work proposed here has the high potential to identify new therapeutic directions for targeting prostate cancer cells and achieving more efficacious approaches to preventing, staging, and treating prostate cancer.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

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[A, Approved For Public Release]