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Accession Number ADA566856
Title Targeting Breast Cancer Recurrence via Hedgehog-mediated Sensitization of Breast Cancer Stem Cells.
Publication Date Jul 2011
Media Count 11p
Personal Author D. J. Robbins J. DiRenzo
Abstract The purpose of the research supported by this award is to determine if targeting the hedgehog signaling pathway in breast cancer can reduce breast cancer recurrence. Two specific facts about breast cancer recurrence highlight the need for better treatment modalities that target and prevent disease recurrence. In the United States and other countries with access to advanced cancer care, local and distant breast cancer recurrence accounts for approx. 95% of breast cancer mortality(Jemal et al., 2010). The life-time risk of breast cancer recurrence among survivors is greater than the lifetime risk of developing breast cancer in the general population(Jemal et al., 2010). Together these two statements suggest that while substantial progress has been made in treating primary breast cancer, those treatments do not efficiently reduce the risk of disease recurrence. Therefore there is a need for novel treatment strategies. Disease recurrence is believed to be the result of a subset of tumor cells with two distinct features; broad spectrum resistance to therapeutics and tumorigenicity(Hurt and Farrar, 2008; Pardal et al., 2003; Polyak and Weinberg, 2009; Woodward et al., 2005). Our previous studies identified a regulatory relationship between Np63 a protein that is required for long-term preservation of epithelial stem cells(Mills et al., 1999; Yang et al., 1999) and the hedgehog-signaling pathway that governed stem cell quiescence(Li et al., 2008). Stem cell quiescence is necessary to preserve long- term replicative capacity while simultaneously avoiding the detrimental effects of excessive proliferation. It is also a potent blockade to cellular differentiation(Coller et al., 2006). Based upon this we put forth the hypothesis that the hedgehog signaling pathway could be targeted to subvert quiescence in stem cell populations. Doing so would force these cells back into the cell cycle, thereby sensitizing them to adjuvant cancer therapeutics.
Keywords Breast cancer
Life span(Biology)
Stem cells

Source Agency Non Paid ADAS
NTIS Subject Category 57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Miami Univ., FL.
Document Type Technical report
Title Note Annual rept. 15 Jun 2010-14 Jun 2011.
NTIS Issue Number 1307
Contract Number W81XWH-10-1-0430

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