12^th World Cancer Conference

The combination of procarbazine, lomustine and vincristine (PCV) is the most commonly used chemotherapy in brain cancer. Th e alkylating agent TMZ is another therapeutic approach used for the treatment of both low and high grade

astrocytic tumors, largely replacing the PCV treatment, as a result of its oral administration and minor side eff ects. However, the enthusiasm for TMZ treatment decreased successively since it became clearly that the TMZ treatment provides survival benefits only for a subgroup of patients that have an altered O6-methylguanine-DNA methyltransferase (MGMT). In addition

to MGMT, many other molecules that regulate tumor growth and survival have been suggested to interfere with brain tumor cells response to TMZ. Several growth factor receptor family members are overexpressed or over activated in glioma, playing an important role in treatment resistance. EGFR dysfunction is considered as one of the most common causes of TMZ therapy failure in glioma patients. In this paper, we aim to determine the eff ect of EGFR inactivation on glioma cells response to TMZ treatment. GB1B and AC1B glioma cell lines used in this study were low passage cultures established from fresh tissues obtained from consented glioma patients undergoing surgery at the “Bagdasar–Arseni” Hospital, Bucharest. Cell viability was quantified by hemocytometer cell counting, using trypan blue. Interactions between TMZ and EGFR inhibitor were classified by the multiplicative model. We found that TMZ inhibits cell viability in human glioma cells in vitro. TMZ, administered alone as a single-dose treatment, induced a persistent cell death in grade II astrocytoma (AC1B cell line) and in glioblastoma (GB1B cell line), 15 days aft er the treatment. We also found out that TMZ eff ect was more preeminent in glioblastoma than in low grade astrocytoma. AG556, an EGFR substrate-site competitor that belongs to the class of low molecular weight compounds,

induced cell growth inhibition in GB1B and AC1B cells, but glioblastoma GB1B cells were significantly more sensitive to EGFR inhibition than low grade astrocytoma AC1B cells. Unexpected, in AC1B cells that were minor sensitive to TMZ or AG556 single treatment, the action of the two drugs together generated synergistic or additive response in the most of the treatment

combinations. In summary, we found that both TMZ and AG556 treatment decreased GB1B and AC1B cells viability. Our results also indicated that TMZ or AG556 treatment alone was more effi cient in inducing cytotoxicity in GB1B cells while the drugs concomitant administration was more potent in AC1B cell line. Th ese fi ndings may help to improve the design of coming clinical trials for evaluating the eff ect of EGFR inactivation on TMZ sensitization in glioma patients.