GLIA-Deep: Glioblastoma Image Analysis using Deep Learning Convolutional Neural Networks to Accurately Classify Gene Methylation and Predict Drug Effectiveness

Glioblastoma multiforme is a deadly brain cancer with a median patient survival time of 18-24 months, despite aggressive treatments. This limited success is due to a combination of aggressive tumor behavior, genetic heterogeneity of the disease within a single patient’s tumor, resistance to therapy, and lack of precision medicine treatments. A single specimen using a biopsy cannot be used for complete assessment of the tumor’s microenvironment, making personalized care limited and challenging.

Temozolomide (TMZ) is a commercially approved alkylating agent used to treat glioblastoma, but around 50% of temozolomide-treated patients do not respond to it due to the over-expression of O6-methylguanine methyltransferase (MGMT). MGMT is a DNA repair enzyme that rescues tumor cells from alkylating agent-induced damage, leading to resistance to chemotherapy drugs. Epigenetic silencing of the MGMT gene by promoter methylation results in decreased MGMT protein expression, reduced DNA repair activity, increased sensitivity to TMZ, and longer survival time. Thus, it is paramount that clinicians determine the methylation status of patients to provide personalized chemotherapy drugs. However, current methods for determining this via invasive biopsies or manually curated features from brain MRI (Magnetic Resonance Imaging) scans are time- and cost- intensive and have a very low accuracy.

Author(s): Viraj Mehta

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