Type

Journal Article

Authors

Jochen H M Prehn
Heiko Düssmann
Norma O'Donovan
Andreas U Lindner
Federico Lucantoni

Subjects

Pharmacology

Topics
synergism apoptosis triple negative breast cancer cancer cells agents lymphoma b cell inhibitors bcl 2

Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells. (2017)

Abstract Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells by BCL2 inhibitors. Using absolute protein levels of BAX, BAK, BCL2, BCL(X)L and MCL1 as input for DR_MOMP, we found a strong correlation between model predictions and responses of a panel of TNBC cells to 24 and 48 h cisplatin (R
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Heiko Düssmann, Norma O'Donovan, Andreas U Lindner, Federico Lucantoni

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
3
Norma O'Donovan
Dublin City University
Total Publications: 59
 
4
Andreas U Lindner
Royal College of Surgeons in Ireland
Total Publications: 13