TMIC-76. GLIOBLASTOMA VESSEL CO-OPTION OCCURS AS A RESISTANCE MECHANISM TO CHEMORADIATION VIA INDUCTION OF A NOVEL CELL STATE

• DOI: 10.1093/neuonc/noad179.1141
• Publication Date: 2023-11-11T23:24:07Z
• Authors: Aafrin M Pettiwala; Cathy Pichol-Thie...; Oceane Anezo; Guillaume Bourmeau; Remi Montagne; Anne-Marie Lyne; Pierre-Olivier Gu...; Pauline Deshors; Alberto Ballestin; Benjamin Blanchard; Vidhya M Ravi; Kevin Joseph; Dieter Henrik Hei...; Boris Julien; Sophie Leboucher; Laetitia Besse; Patricia Legoix; Charita Furumaya; Laura Kovandzic M...; Konstantin Maslia...; Thomas Daubon; Oliver Schnell; Jürgen Beck; Nicolas Servant; Lucie Karayan-Tapon; Florence Cavalli; Giorgio Seano
• Keywords: 0301 basic medicine; 03 medical and health sciences

Abstract Glioblastoma (GB) is one of the deadliest types human cancer. Despite a very aggressive treatment regime-including resection, chemo-radiation, its recurrence rate more than 90%. Recurrence mostly caused by highly resistant and invasive cells that spread from tumor bulk are not removed resection. To develop an effective therapeutic approach, we need to better understand underlying molecular cellular mechanism driving therapy resistance invasion in GB. dynamically track changes post-therapy chemoradiation-resistant cells, employed multiple single cell transcriptomics, phosphoproteome, vitro vivo real time imaging, organotypic cultures, functional analysis, digital pathology spatial transcriptomics on patient material preclinical models We demonstrated chemoradiation brain vasculature induce transition state, which rename as VC-Resist. Better survival, G2M arrest, senescence/stemness pathway induction, makes this GB state much resistant. Notably, these vessel co-opting allowing homing perivascular niche, turn increases their state. Molecularly, VC-Resist takes place through FGF-FGFR1 signaling leads activation DNA damage repair, YAP Rho pathways. These findings demonstrate niche plasticity jointly generates vicious loop infiltration during recurrence.