DDDR-07. EVALUATING THE ROLE OF THE PIK3CB PATHWAY IN TEMOZOLOMIDE RESISTANCE IN GLIOBLASTOMA USING THE GENOMICS OF DRUG SENSITIVITY IN CANCER (GDSC) AND CANCER CELL LINE ENCYCLOPEDIA (CCLE) DATABASES

Abstract Glioblastoma multiforme (GBM) is a lethal primary brain cancer with median survival of 14.6 months despite standard treatment maximal surgical resection, radiotherapy, and temozolomide (TMZ). Recent research has identified PIK3CB/p110β as the most important regulator AKT activation GBM cell survival. Utilizing pharmacogenomic databases Genomics Drug Sensitivity in Cancer (GDSC) Cell Line Encyclopedia (CCLE), we sought to elucidate relationship between PIK3CB mRNA expression or phosphorylation resistance. We first lines matched PI3K isoform expression, protein (AKT at S473 T308; reverse phase array) drug sensitivity (defined by area under curve; AUC) from GDSC1 CCLE databases. Associations isoforms, phosphorylation, sensitivities were reported fitting univariable multivariable linear regression models without interaction terms communicate effects conditional on levels. found that data together performed better biomarker predicting therapeutic response p110β-selective inhibitors than each variable alone, specifically T308 was negatively related inhibitor AZD6482 low levels (B = -0.069, p 0.0513) this disappeared higher 0.04, 0.176) an near statistical significance (p 0.0674). significantly positively associated TMZ resistance (B=0.019, p=0.0211) while other isoforms not. While currently used for pathway inhibitors, study, demonstrate both significant p110β compared assessing independently. Furthermore, implicated catalytic isoforms.