Type

Other / n/a

Authors

Brona M Murphy
Markus Rehm
Grainne Johnston
Frank A Lincoln
Maximilian L Würstle
Janis Noonan
Birgit C Weyhenmeyer

Subjects

Biochemistry

Topics
glioblastoma trail cancer drug resistance apoptosis temozolomide systems biology physiology physics

Predicting the cell death responsiveness and sensitization of glioma cells to TRAIL and temozolomide. (2016)

Abstract Genotoxic chemotherapy with temozolomide (TMZ) is a mainstay of treatment for glioblastoma (GBM); however, at best, TMZ provides only modest survival benefit to a subset of patients. Recent insight into the heterogeneous nature of GBM suggests a more personalized approach to treatment may be necessary to overcome cancer drug resistance and improve patient care. These include novel therapies that can be used both alone and with TMZ to selectively reactivate apoptosis within malignant cells. For this approach to work, reliable molecular signatures that can accurately predict treatment responsiveness need to be identified first. Here, we describe the first proof-of-principle study that merges quantitative protein-based analysis of apoptosis signaling networks with data- and knowledge-driven mathematical systems modeling to predict treatment responsiveness of GBM cell lines to various apoptosis-inducing stimuli. These include monotherapies with TMZ and TRAIL, which activate the intrinsic and extrinsic apoptosis pathways, respectively, as well as combination therapies of TMZ+TRAIL. We also successfully employed this approach to predict whether individual GBM cell lines could be sensitized to TMZ or TRAIL via the selective targeting of Bcl-2/Bcl-xL proteins with ABT-737. Our findings suggest that systems biology-based approaches could assist in personalizing treatment decisions in GBM to optimize cell death induction.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> RCSI Undergraduate Research
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics
Ireland -> Royal College of Surgeons in Ireland -> RCSI Undergraduate Research Articles

Full list of authors on original publication

Brona M Murphy, Markus Rehm, Grainne Johnston, Frank A Lincoln, Maximilian L Würstle, Janis Noonan, Birgit C Weyhenmeyer

Experts in our system

1
Brona M Murphy
Royal College of Surgeons in Ireland
Total Publications: 14
 
2
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55
 
3
Frank A Lincoln
Royal College of Surgeons in Ireland
Total Publications: 3
 
4
Maximilian L Würstle
Royal College of Surgeons in Ireland
Total Publications: 13
 
5
Janis Noonan
Royal College of Surgeons in Ireland
Total Publications: 6
 
6
Birgit Weyhenmeyer
Royal College of Surgeons in Ireland
Total Publications: 6