MEDICINA BUENOS AIRES VOL. 77 Supl. I - Antitumor effect of Rac1 inhibitor 1A-116 in combination with temozolomide in glioblastoma multiforme

Congreso

Resumen *

Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration and proliferation. The aberrant activation of Rac1 GTPase is involved in tumor progression, invasion and chemoresistance in brain tumors. Rac1 is hyperactivated in glioblastoma cells and Rac1 appears to be a suitable target for the development of novel anticancer therapies. Rac1 inhibitors as monotherapy or in combinational settings with traditional chemotherapy such as Temozolomide (TMZ) could have a profound effect on the disease progression. We analysed the gene expression profiles from Gene Expression Omnibus (GEO) database and found a high correlation between Rac1 expression and poor patient outcome in 80 glioblastoma patient samples. We also examined MGMT expression, the major biomarker for this tumor type, but it did not correlate with patient outcome in our analysis. We tested the effect of 1A116 in vitro, a novel Rac1 inhibitor developed by our group, on a panel of neural tumor cell lines.1A116 showed IC50 values between 9 M and 30 M. We also tested TMZ effect on the same cell panel, showing IC50 values between 100 M and over 500 M depending on MGMT status. We combined both drugs and found an interesting cooperative effect. These results show the potential use of Rac1 inhibitor 1A116 as therapeutic agent in combination with TMZ for glioblastoma treatment Información suministrada por el agente en SIGEVA