2004
DOI: 10.1016/j.ccr.2004.08.019
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Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/−p53−/− mice

Abstract: Medulloblastoma is the most common malignant pediatric brain tumor. Current treatment is associated with major long-term side effects; therefore, new nontoxic therapies, targeting specific molecular defects in this cancer, need to be developed. We use a mouse model of medulloblastoma to show that inhibition of the Sonic Hedgehog (Shh) pathway provides a novel therapy for medulloblastoma. A small molecule inhibitor of the Shh pathway, HhAntag, blocked the function of Smoothened in mice with medulloblastoma. Thi… Show more

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Cited by 486 publications
(414 citation statements)
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“…Notch and Sonic Hedgehog (Shh) pathways have been previously found to have important roles in the maintenance of several types of tissue, including prostate Karhadkar et al 2004;Wang et al 2006). Modulation of the Shh pathway with cyclopamine has also been shown to decrease the growth of medulloblastoma (Romer et al 2004) and prostate cancer ) in mouse models. Now that we have the ability to isolate a highly enriched PrSC fraction, our immediate goal is to identify novel pathways that confer long-term self-renewal to these cells and test whether their modulation can control the progression of prostate cancer.…”
Section: Discussionmentioning
confidence: 99%
“…Notch and Sonic Hedgehog (Shh) pathways have been previously found to have important roles in the maintenance of several types of tissue, including prostate Karhadkar et al 2004;Wang et al 2006). Modulation of the Shh pathway with cyclopamine has also been shown to decrease the growth of medulloblastoma (Romer et al 2004) and prostate cancer ) in mouse models. Now that we have the ability to isolate a highly enriched PrSC fraction, our immediate goal is to identify novel pathways that confer long-term self-renewal to these cells and test whether their modulation can control the progression of prostate cancer.…”
Section: Discussionmentioning
confidence: 99%
“…In these mice, reduced progenitor cell number was correlated with a marked increase in apoptosis (Machold et al, 2003). Other examples of Hh regulating proliferation and cell death are illustrated in studies on different types of cancer (Qualtrough et al, 2004;Romer et al, 2004;Sanchez et al, 2004;Sanchez and Ruiz i Altaba, 2005). Likewise, Hh signaling is also involved in progenitor cell proliferation and survival during eye development in several different organisms (Stenkamp et al, 2002, and reviewed in Amato et al, 2004Wang et al, 2005).…”
Section: Regeneration Stimulated By Fgf2 Requires Basal Levels Of Hh mentioning
confidence: 96%
“…The p53 pathway and Hh signaling are two major alterations in BCCs and medulloblastomas, leading to speculation that the p53 pathway collaborates with Hh signaling in carcinogenesis. Indeed, almost all Ptch1 þ /À mice in p53 null background develop medulloblastomas, BCCs and other tumor types whereas Ptch1 þ /À mice in p53 wildtype background have a low frequency of tumor development (Romer et al, 2004;Epstein, 2008). Recent studies reveal that Hh signaling overrides p53-mediated signaling through regulation of MDM2, and p53 negatively regulates Gli1 expression (Abe et al, 2008;Stecca and Ruiz i Altaba, 2009).…”
Section: Interactions Between Hedgehog Signaling and Other Pathwaysmentioning
confidence: 99%