The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response

Maurizio Martini, Alessandro Olivi, Ruggero De Maria Marchiano, Luigi Maria Larocca, Roberto Pallini, Quintino Giorgio D'Alessandris, Tonia Cenci, Mauro Biffoni, Daniele Runci, Mariachiara Buccarelli, Michele Signore, Louis Stancato

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

22 Citazioni (Scopus)

Abstract

Background. Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblas- toma (GBM) biology, do not in uence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods. The relationship betweenTS growth and clinical outcome was investigated in 52 GBMs treated with sur- gical resection followed by radiotherapy and temozolomide (TMZ).The effect onTS of radiation (6 to 60 Gy) and of TMZ (3.9 μM to 1 mM) was related with patients’ survival. Results. Generation of TS was an independent factor for poor overall survival (OS) and poor progression-free survival (PFS) (P < .0001 and P = .0010, respectively). Growth rate and clonogenicity ofTS predicted poor OS. In general,TS were highly resistant to both radiation andTMZ. Resistance toTMZ was stronger inTS with high clono- genicity and fast growth (P < .02). Shorter PFS was associated with radiation LD50 (lethal dose required to kill 50% ofTS cells) >12 Gy of matchedTS (P = .0484). A direct relationship was found between sensitivity ofTS toTMZ and patients’ survival (P = .0167 and P = .0436 for OS and PFS, respectively). Importantly, values forTMZ half-maximal inhibitory concentration <50 μM, which are in the range of plasma levels achieved in vivo, identi ed cases with longer OS and PFS (P = .0020 and P = .0016, respectively). Conclusions. Analysis ofTS holds translational relevance by predicting the response of parent tumors to radiation and, particularly, to TMZ. Dissecting the clonogenic population from proliferating progeny in TS can guide thera- peutic strategies to a more effective drug selection and treatment duration.
Lingua originaleEnglish
pagine (da-a)1097-1108
Numero di pagine12
RivistaNeuro-Oncology
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • glioblastoma

Fingerprint Entra nei temi di ricerca di 'The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response'. Insieme formano una fingerprint unica.

Cita questo