Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449
By C. Rudin, C. Hann, J. Laterra, R. Yauch, C. Callahan, L. Fu, Thomas Holcomb, Jeremy Stinson, S. Gould, B. Coleman and 4 more. New England Journal of Medicine, 2009
1,018 citations recorded by the source corpus.
SUMMARY Medulloblastoma is the most common malignant brain tumor in children. Aberrant activation of the hedgehog signaling pathway is strongly implicated in the development of some cases of medulloblastoma. A 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies was treated with a novel hedgehog pathway inhibitor, GDC-0449; treatment resulted in rapid (although transient) regression of the tumor and reduction of symptoms. Molecular analyses of tumor specimens obtained before treatment suggested that there was activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched homologue 1 (PTCH1), a key negative regulator of hedgehog signaling.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2ec062ee730431afa2dbf27878a5d2260aef53bf
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In Genetics
In Molecular Biology
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Citations in the corpus
- Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition (2014, background): “Furthermore, as has been shown in both humans and mice, tumors may also rapidly acquire secondary resistance to treatment (Dijkgraaf et al., 2011; Rudin et al., 2009; Yauch et al., 2009), suggesting that such inhibitors might be ineffective as a curative option when administered as monotherapy.”
- G protein-coupled receptors: novel targets for drug discovery in cancer (2010, background): “However, in a patient enrolled in the GDC-0449 Phase I study, the metastatic medulloblastoma relapsed after an initially rapid but incomplete respons”
- Molecular subgroups of medulloblastoma: the current consensus (2011, background): “The recent demonstration that small molecules targeting smoothened (SMO) are highly effective, albeit temporarily, against Shh medulloblastoma underlines the urgent need to develop effective and practical markers for Shh medulloblastoma [6, 40, 49].”