In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 16, No. 10_Supplement ( 2017-10-01), p. B14-B14
Abstract:
Glioblastoma (GBM) is the most aggressive and common form of adult brain cancer and is among the deadliest cancers, with a median survival of 15 months using standard-of-care therapies. Thus, improved treatments for GBM are desperately needed. To identify new GBM molecular therapeutic targets, our group has performed multiple functional genetic screens in patient-derived GBM stem-like cells (GSCs) and non-transformed human neural stem and progenitor cells (NPCs), which represent non-neoplastic controls. These screens, which have used both RNAi and CRISPR-Cas9 platforms, have led to the identification of several key molecular vulnerabilities in GSCs, including GBM-specific defects in: 3' splice site recognition, kinetochore function, and loss of redundancy between the kinase activities of PKMYT1 and WEE1. At this meeting we will present an overview of these studies, as well as our current efforts to: comprehensively retest all GBM-specific vulnerabilities scoring in these screens; address whether vulnerabilities arise from specific genetic alterations in patient samples (e.g. NF1 loss or PTEN loss); determine whether inhibition of specific molecular targets blocks tumor growth and/or maintenance; and demonstrate the mode of GBM-specific death for particular targets (e.g., cell cycle arrest, apoptosis, etc). In addition, we will highlight both strengths and limitations of applications of CRISPR-Cas9 technologies in patient samples. Collectively, our work illustrates the power of combining functional genetic technologies with the use of patient isolates to identify novel, patient-specific therapeutic strategies for GBM. Citation Format: Pia Hoellerbauer, Heather Feldman, Sonali Arora, Lucas Carter, Emily J. Girard, Philip Corrin, James M. Olson, Eric C. Holland, Patrick J. Paddison. Precision functional genomics for glioblastoma: Identifying molecular therapeutic targets using CRISPR-Cas9 and RNAi technologies in patient isolates [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B14.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1538-8514.SYNTHLETH-B14
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2062135-8
SSG:
12
