Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma.

Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma.
Oncotarget. 2018 Oct 09;9(79):34935-34944
Authors: Da Ros M, Iorio AL, De Gregorio V, Fantappiè O, Laffi G, de Martino M, Pisano C, Genitori L, Sardi I
Abstract
Glioblastoma Multiforme (GBM) is still an incurable disease. The front-line Temozolomide (TMZ)-based therapy suffers from poor efficacy, underlining the need of new therapies. Preclinically, Aldoxorubicin (Aldox), a novel prodrug of Doxorubicin (Dox), has been successfully tested against GBM, encouraging the study of its association with other agents. For the first time, we evaluated the effectiveness of Aldox combined to TMZ in preclinical models of GBM. Our in vitro results demonstrated that the anti-glioma effect of Aldox was more marked than TMZ and their combination increased the killing effect of the anthracycline in TMZ-resistant GBM cells. Moreover, unlike Dox, Aldox was able to accumulate in P-glycoprotein (P-gp)-overexpressed cells due to a negative regulation of the P-gp function. We also compared efficacy and safety of weekly administrations of Aldox (16 mg/kg), with or without TMZ (0.9 mg/kg, daily injections), in the U87 xenograft mouse model. Aldox therapy induced a moderate tumor volume inhibition (TVI) and an increased survival rate (+12.5% vs vehicle). On the other hand, when combined to TMZ, Aldox caused a significant TVI (P=0.0175 vs vehicle) and delayed the mortal...

Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research