Abstract 4307: In vitro drug sensitivity and genetic profile analysis from primary culture obtained from brain cancer

Abstract

The Cancer Genome Atlas effort subtyped gliomas in four molecular groups based on gene expression, mutation and deletion and retrospectively linked these subtypes to chemotherapy response. But up to now there is no protocol to use this or other methods to predict chemotherapy response in the clinic for gliomas. Patients are normally treated with ratiotherapy and temozolomide (TMZ) in a protocol of 5 days of treatment and 23 days of recovery. The goal of this study is to analyze gene expression and drug sensitivity in a relevant time frame to prospectively contribute to therapeutic decisions. For this, we prepared 19 cell cultures from 19 biopsies of brain tumors and treated them with a range of chemotherapy agents (TMZ, carmustine, lomustine, cisplatin, etoposide, paclitaxel, irinotecan, procarbazin, mebendazol, vincristin and vinblastin) at plasmatic concentration. Cells were counted for at least 12 days after treatment or tested for viability after 7 or 14 days and more that 60% reduction was considered a positive response. From eleven cell cultures tested with viability assay, only one responded to temozolomide (the first line chemotherapy for this tumor) after a single administration. The strongest effect was obtained using anti-microtubule agents. Cell counting after 12 days of treatment confirmed the resistance to TMZ and the sensitivity to antimicrotubule drugs, particularly paclitaxel. Combination of procarbazin, lomustine and vincristine (PCV), previously used to treat glioblastoma patients, killed very effectively cells of only 1 patient. The cell cultures from three of five patients display EGFR over-expression and four of five presented p53 and p21 expression. At this time, we are not able to correlate gene expression, subtyping and drug sensitivity. From these data we conclude that brain tumors can be routinely grown and tested for drug sensitivity in a time frame that more closely mimics the treatment of patients. Ethical protocol number UFRGS: 420.856; PUCRS: 429.849 Financial support: FAPERGS, CNPq e CAPES. Citation Format: Franciele C. Kipper, Louise C. Mendonça, Rafael Becker, Gláucia Confortin, Pítia F. Ledur, André Marc, Eliseu Paglioli-Neto, Fabiana Viola, Fernanda B. Morrone, Guido Lenz. In vitro drug sensitivity and genetic profile analysis from primary culture obtained from brain cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4307. doi:10.1158/1538-7445.AM2015-4307