A sequential targeting strategy interrupts AKT-driven subclone-mediated progression in glioblastoma.
Sied KebirVivien UllrichPia BergerCelia DobersalskeSarah LangerLaurèl RauschenbachDaniel TrageserAndreas TillFranziska K LorbeerAnja WielandTimo Wilhelm-BuchstabAshar AhmadHolger FröhlichIgor CimaShruthi PrasadJohann MatschkeVerena JendrossekMarc RemkeBarbara M GrünerAlexander RoeschJens Thomas SivekeChristel Herold-MendeTobias BlauKathy KeyvaniFrank K H van LandeghemTorsten PietschJörg FelsbergGuido ReifenbergerMichael WellerUlrich SureOliver BrüstleMatthias SimonMartin GlasBjörn SchefflerPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2022)
Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to temozolomide therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of temozolomide and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation.