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posted by martyb on Saturday August 31 2019, @10:02AM   Printer-friendly
from the flowers-for-Algernon dept.

Arthur T Knackerbracket has found the following story:

One of the most common brain cancers in children, Sonic Hedgehog (SHH) medulloblastoma, also is one of the more survivable for most kids. Unfortunately, for a subset of patients the cancer resists treatment and relapses with a vengeance to then turn deadly.

Researchers at Cincinnati Children's Hospital Medical Center used a powerful new computer-assisted technology called single-cell transcriptomics that measures thousands of individual cells simultaneously to map cell types and molecular cascades that drive the growth of SHH-medulloblastoma. In a study published Aug. 29 by the journal Cancer Cell, the scientists report they discovered new treatment strategies for the disease that may help patients fight a recurrent cancer.

Scientists used direct genetic manipulation to block genetic and molecular cascades they discovered in SHH-medulloblastoma tumors. The genetic-molecular block stopped the cancer growth and prevented relapse in tumor-forming laboratory mice, according Q. Richard Lu, PhD, a senior study investigator and scientific director of the Brain Tumor Center at Cincinnati Children's.

"Medulloblastoma is driven by a diverse group of cell types and molecular pathways that haven't been understood very well," said Lu. "But after identifying the molecular triggers and potential cells of origin for tumor initiation and recurrence, we determined from further testing that there are existing small molecule inhibitors that can target the oncogenic cascade pathways that cause SHH tumor initiation and recurrence."

The researchers developed their new data by subjecting SHH-medulloblastoma tumors in lab animals at various stages of tumor growth to single-cell transcriptomic analysis. The technique generated an extensive dataset that identifies the complete set of transcribed DNA sequences in every single cancer cell. The scan revealed that immature oligodendrocyte progenitor cells in the brain -- which can assume stem-cell-like qualities -- grow out of control to form medulloblastoma tumors and the molecular cascade that fuels recurring brain cancer.

Although additional preclinical research is need before clinical testing can be proposed for patients, the current study points to several molecular targets that respond to combined treatment with existing drugs, according to study co-lead author Xuelian He, MD, PhD, a former member of the Lu laboratory and now at Boston Children's Hospital. Combination therapies allow lower drug doses and improved drug tolerability for patients while achieving a certain level of therapeutic efficacy.

Liguo Zhang, et. al. Single-Cell Transcriptomics in Medulloblastoma Reveals Tumor-Initiating Progenitors and Oncogenic Cascades during Tumorigenesis and Relapse. Cancer Cell, 2019; DOI: 10.1016/j.ccell.2019.07.009


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