Targeting Pediatric Glioma with Apoptosis and Autophagy Manipulation
Abstract
Gliomas are the most common and most deadly solid tumors that affect children. Treatment options are limited and cure rates are dismal. My laboratory has established that Mer and Axl receptor tyrosine kinase are aberrantly overexpressed in gliomas, and that inhibition of these RTKs leads to increased glioma cell apoptosis, decreased tumor cell survival and profoundly improved chemosensitivity. However, I have also recognized that Mer and Axl inhibition is associated with increased autophagy, and most recently we have found this is true in several glioma cell lines, including one of pediatric origin. I hypothesize that Mer and Axl RTK signaling regulates autophagy pathway activation in glioma cells, and this regulation determines the efficiency of glioma cell killing. We have found that Mer signaling downregulation in combination with inhibition of late stage autophagy. cycling leads to decreased colony formation at three weeks in soft agar. Understanding the effects of autophagy manipulation in the setting of tyrosine kinase inhibition will help us design the most appropriate approach to targeted therapeutics for glioma and allow us to develop a clinical trial that adequately addresses both apoptosis and autophagy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2012
- Accession Number
- ADA567861
Entities
People
- Amy Keating
Organizations
- University of Colorado Boulder