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Rational targeting of dynamic tumor subclones in relapsing human glioblastoma

ABSTRACT: Glioblastoma therapy relies on the alkylating drug temozolomide (TMZ) administered to irradiated patients post-neurosurgery, which increases overall survival but cannot prevent fatal disease relapse. Using clinical samples and glioblastoma models, we here identify TMZ-driven enrichment of ALDH1A1+ tumor subclones acquiring AKT-dependent drug resistance en route to relapse. We demonstrate that this recurrent phenotype switch is predictable and can be countered by a sequential rather than simultaneous combinatorial treatment approach.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145128 | GEO | 2020/02/12

REPOSITORIES: GEO

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