SPECIFIC INHIBITION OF PROSURVIVAL FACTOR Bcl-xL DISTINCTLY SENSITIZES PATIENT DERIVED GLIOMA STEM CELL LINES TO CHEMOTHERAPY DRUGS

NOGUEIRAS, GERMÁN IGNACIO; FURMENTO, VERÓNICA ALEJANDRA; MORRIS HANON, OLIVIA; SEVLEVER, GUSTAVO EMILIO; SCASSA, MARÍA ELIDA; VIDELA-RICHARDSON, GUILLERMO AGUSTÍN

Congreso; Reunión de Sociedades de Biociencia 2017; 2017

High-grade gliomas are the most prevalent and lethal primary brain tumors for which the cure rate remains extremely low. They display a hierarchical arrangementwith a population of self-renewing and highly tumorigenic cells called cancer stem cells. High levels of anti-apoptotic molecules in cancer cells have been shown to both result inresistance to chemotherapy and promotion of unrestrained growth. BH3 mimetics inhibit anti-apoptotic Bcl-2 family members and are currently under clinical trials as potentialcandidates for cancer treatment. The aim of this study was to determine the sensitivity of individual patient-derived glioma stem cell enriched cell lines (GSC-ECLs)to molecules targeting anti-apoptotic Bcl-2 members to identify potential druggable biomarkers that may help design highly effective combination therapies. To achieve ourobjectives, we examined the sensitivity of GSC-ECLs, previously established in our laboratory, to a panel of chemotherapeutic drugs (temozolamide, lomustine and vincristine)both alone or in combination with the BH3 mimetics: ABT-263 (inhibitor of Bcl-2, BclxL and Bcl-W) or WEHI-539 (specific inhibitor of Bcl-xL) or with small interfering RNA(siRNA) oligonucleotides specifically targeting Bcl-xL, Bcl-2 or Bcl-W.