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The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.
View the Table of Contents for the June 15 issue of Cancer Research.
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Zhang and colleagues have identified a tumorigenic subpopulation characterized as Lin–CD29HCD24H within a unique p53-null mammary tumor model as demonstrated by limiting dilution transplantation experiments into the cleared mammary fat pads of syngeneic mice. Microarray analysis suggests that genes involved in epigenetic regulation play an important role in regulating the cell fate of these tumor-initiating cells. Increased expression of DNA damage response genes may help explain the resistance of cancer stem cells to chemo- and radiation therapy, and provides a basis for future studies designed to decrease therapeutic resistance and improve treatment outcome.
Placencio et al. Page 4709 Patients with prostate cancer unresponsive to androgen ablation therapy are left with limited treatment options. Placencio and colleagues studied the cooperation between TGF-β, androgen, and Wnt signaling on mouse models aimed at understanding the regression of the prostate following androgen ablation. These studies highlight the importance of stromal TGF-β signaling in regulating paracrine Wnt signaling as a contributor to androgen independence of the prostate epithelia. The cross-talk of stromal-epithelial signaling demonstrates the potential use of a suppressor of the canonical Wnt signaling pathway to augment androgen ablation therapy.
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Hilberg et al. Page 4774 Signals mediated by receptors for VEGF, FGF, and PDGF are known to contribute to tumor angiogenesis, suggesting that inhibition of these pathways could be of clinical benefit. Hilberg and colleagues demonstrate that the novel indolinone derivative BIBF 1120 potently inhibits the activity of these angiokinases. BIBF 1120 binds to the ATP pocket as evidenced by the structure of cocrystals with the VEGFR-2 kinase. In cell culture, BIBF 1120 inhibits angiokinase signaling pathways and affects proliferation and survival of endothelial cells, pericytes, and smooth muscle cells. In human tumor xenograft models in mice, BIBF 1120 administered orally inhibits angiogenesis, tumor perfusion, and tumor growth. This compound is currently being investigated in advanced clinical trials in cancer patients.
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