Medicina Buenos Aires - ANTITUMOR EFFECT OF RAC1 INHIBITOR 1A116 IN COMBINATION WITH TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME

Congreso

Resumen *

Rho GTPases represent a family of small GTP-binding proteinsinvolved in cell cytoskeleton organization, migration and proliferation.The aberrant activation of Rac1 GTPase is involved in tumorprogression, invasion and chemoresistance in brain tumors. Rac1is hyperactivated in glioblastoma cells and Rac1 appears to be asuitable target for the development of novel anticancer therapies.Rac1 inhibitors as monotherapy or in combinational settings withtraditional chemotherapy such as Temozolomide (TMZ) could havea profound effect on the disease progression.We analysed the gene expression profiles from Gene ExpressionOmnibus (GEO) database and found a high correlation betweenRac1 expression and poor patient outcome in 80 glioblastomapatient samples. We also examined MGMT expression, the majorbiomarker for this tumor type, but it did not correlate with patient outcomein our analysis. We tested the effect of 1A116 in vitro, a novelRac1 inhibitor developed by our group, on a panel of neural tumorcell lines.1A116 showed IC50 values between 9 mM and 30 mM. Wealso tested TMZ effect on the same cell panel, showing IC50 valuesbetween 100 mM and over 500 mM depending on MGMT status. Wecombined both drugs and found an interesting cooperative effect.These results show the potential use of Rac1 inhibitor 1A116 astherapeutic agent in combination with TMZ for glioblastoma treatment. Información suministrada por el agente en SIGEVA