Modeling Signaling Networks to Advance New Cancer Therapies

Annu Rev Biomed Eng. 2015:17:143-63. doi: 10.1146/annurev-bioeng-071813-104927. Epub 2015 Aug 14.

Abstract

Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3' kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer.

Keywords: cancer; mathematical modeling; signal transduction; systems pharmacology; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • MAP Kinase Signaling System / genetics
  • Models, Biological*
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction

Substances

  • Phosphatidylinositol 3-Kinases