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Combining systems biology models of apoptosis provides superior predictions of the responsiveness of melanoma cells to cell death inducing drugs

  • Paul Curtayne1,
  • Maximilian Wuerstle2,
  • Andreas Lindner2,
  • Jochen Prehn2 and
  • Markus Rehm2
BMC Proceedings20159(Suppl 7):A10

Published: 27 October 2015


MelanomaMelanoma CellApoptotic Cell DeathMitochondrial Outer MembraneApoptosis Pathway


Key to the clinical management of melanoma is the development of new diagnostic tools that predict individual patient prognosis and select from potential treatments those which may be effective. Identifying individual biomarkers in tumour cells to predict susceptibility to apoptotic cell death has thus far been largely unsuccessful, as apoptosis pathways show a high degree of signalling redundancy.


DR_MOMP [1] and ApoptoCell [2] are mathematical systems biology models of the mitochondrial outer membrane permeabilisation and execution stages of the apoptosis pathway, respectively, that take into account the complex nature of apoptosis regulation. Both models use a network of ordinary differential equations representing measured protein concentrations and reaction kinetics. In this study we combine these models and compare model predictions to experimental measurements of cell death in a range of melanoma cell-lines that were treated with different cytotoxic agents.


The combined approach is found to outperform either individual model in predicting strong and weak responses to treatment with cell death inducing drugs.


This work may provide a basis for the development of improved prediction tools for clinical treatment outcomes and treatment selection in melanoma.

Authors’ Affiliations

Royal College of Surgeons in Ireland, Dublin, Ireland
Centre for Systems Medicine, Dept of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland


  1. Lindner AU, Concannon CG, Boukes GJ, Cannon MD, Llambi F, Ryan D, et al: Systems Analysis of BCL2 Protein Family Interactions Establishes a Model to Predict Responses to Chemotherapy. Cancer Research. 2013, 73 (2): 519-28. 10.1158/0008-5472.CAN-12-2269.PubMedView ArticleGoogle Scholar
  2. Rehm M, Huber HJ, Dussmann H, Prehn JHM: Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein. EMBO J. 252006, 4338-49.Google Scholar


© Curtayne et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.