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Lookup NU author(s): Dr Marina Danilenko, Professor Steven CliffordORCiD, Dr Ed Schwalbe
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© 2021Medulloblastoma is the most common malignant CNS tumor of childhood, affecting ~350 patients/year in the USA. In 2020, most children are cured of their disease, however, survivors are left with life-long late-effects as a consequence of intensive surgery, and application of chemo- and radio-therapy to the developing brain. A major contributor to improvements in patient survival has been the development of risk-stratified treatments derived from a better understanding of the prognostic value of disease biomarkers. The characterization and validation of these biomarkers has engendered a comprehensive understanding of the extensive heterogeneity that exists within the disease, which can occur both between and within tumors (inter- and intra-tumoral heterogeneity, respectively). In this review, we discuss inter-tumoral heterogeneity, describing the early characterization of clinical and histopathological disease heterogeneity, the more recent elucidation of molecular disease subgroups, and the potential for novel therapies based on specific molecular defects. We reflect on the limitations of current approaches when applied to a rare disease. We then review early investigations of intra-tumoral heterogeneity using FISH and immunohistochemical approaches, and focus on the application of next generation sequencing on bulk tumors to elucidate intra-tumoral heterogeneity. Finally, we critically appraise the applications of single-cell sequencing approaches and discuss their potential to drive next biological insights, and for routine clinical application.
Author(s): Danilenko M, Clifford SC, Schwalbe EC
Publication type: Review
Publication status: Published
Journal: Pharmacology and Therapeutics
Year: 2021
Volume: 228
Print publication date: 01/12/2021
Online publication date: 01/03/2021
Acceptance date: 02/04/2018
ISSN (print): 0163-7258
ISSN (electronic): 1879-016X
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.pharmthera.2021.107828
DOI: 10.1016/j.pharmthera.2021.107828
PubMed id: 33662447
