Publications by authors named "S L Markant"

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important.

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Article Synopsis
  • Smoothened (SMO) inhibitors are being tested for treating sonic-hedgehog-driven medulloblastoma (SHH-MB), but patient responses vary widely.
  • A study sequenced 133 SHH-MB cases, finding that PTCH1 mutations were common across all ages, while SUFU mutations primarily appeared in infants and adults had more SMO mutations.
  • Functional tests showed tumors with PTCH1 mutations responded to SMO inhibitors, but those with SUFU mutations or MYCN amplifications were mostly resistant.
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Medulloblastoma is the most common malignant brain tumor in children. Although aggressive surgery, radiation, and chemotherapy have improved outcomes, survivors suffer severe long-term side effects, and many patients still succumb to their disease. For patients whose tumors are driven by mutations in the sonic hedgehog (SHH) pathway, SHH antagonists offer some hope.

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Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neurooncology.

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The WNT pathway plays multiple roles in neural development and is crucial for establishment of the embryonic cerebellum. In addition, WNT pathway mutations are associated with medulloblastoma, the most common malignant brain tumor in children. However, the cell types within the cerebellum that are responsive to WNT signaling remain unknown.

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