Intratumoral Heterogeneity : Pathways to Treatment Resistance and Relapse in Human Glioblastoma
Cet article passe en revue les études sur l'hétérogénéité intratumorale du glioblastome humain, analyse la pertinence des modèles expérimentaux utilisés et suggère l'utilisation des nouvelles technologies pour identifier des populations cellulaires réfractaires aux traitements et développer de nouvelles voies thérapeutiques
Intratumoral heterogeneity (ITH) has increasingly being described for multiple cancers as the root cause of therapy resistance. Recent studies have started to explore the scope of ITH in glioblastoma (GBM), a highly aggressive and fatal form of brain tumor, to explain its inevitable therapy resistance and disease relapse. In this review, we detail the emerging data that explores the extensive genetic, cellular and functional ITH present in GBM. We discuss current experimental models of human GBM recurrence and suggest harnessing new technologies (CRISPR-Cas9 screening, CyTOF, cellular barcoding, single cell analysis) to delineate GBM ITH and identify treatment-refractory cell populations, thus opening new therapeutic windows. We will also explore why current therapeutics have failed in clinical trials and how ITH can inform us on developing empiric therapies for the treatment of recurrent GBM.
Annals of Oncology , résumé, 2016