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Overcoming therapeutic resistance in glioblastoma: the way forward

Satoru Osuka, Erwin G Van Meir

    The Journal of Clinical Investigation
    |February 2, 2017
    PubMed

    Insights

    Glioblastoma recurrence is driven by therapy-resistant, stem-like cancer cells. Targeting genetic alterations and reprogramming in these recurrence-initiating stem-like cancer (RISC) cells is crucial for preventing glioblastoma regrowth.

    Area of Science:

    • Neuro-oncology
    • Cancer genomics
    • Tumor biology

    Background:

    • Glioblastoma is a lethal brain tumor with high recurrence rates.
    • Therapy resistance in glioblastoma leads to patient mortality.
    • Understanding tumor heterogeneity is key to developing new treatments.

    Purpose of the Study:

    • To identify and characterize glioblastoma cells responsible for tumor recurrence.
    • To propose a new nomenclature for these resistant cells.
    • To highlight therapeutic strategies targeting glioblastoma recurrence.

    Main Methods:

    • Analysis of recent genomic studies in glioblastoma.
    • Investigation of tumor heterogeneity and genomic landscape.
    • Characterization of resistant cell properties and pathways.

    Main Results:

    • Genomic studies reveal complex glioblastoma heterogeneity.
    • Resistant cells exhibit stem-like properties and co-opt developmental pathways.
    • These cells, termed recurrence-initiating stem-like cancer (RISC) cells, drive tumor regrowth.

    Conclusions:

    • RISC cells are central to glioblastoma recurrence.
    • Innate and adaptive resistance mechanisms in RISC cells involve genetic alterations and genomic reprogramming.
    • Targeting both resistance mechanisms is essential to prevent glioblastoma recurrence.

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