Adaptation and learning of molecular networks as a description of cancer development at the systems-level: Potential use in anti-cancer therapies

Dávid M. Gyurkó, Dániel V. Veres, Dezsó Módos, Katalin Lenti, T. Korcsmáros, P. Csermely

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapidly proliferating forms may have more rigid, or more plastic networks, respectively. The extremely high ability of cancer stem cells to change the rigidity/plasticity of their networks may be their key hallmark. The application of early stage-optimized anti-cancer drugs to late-stage patients may be a reason of many failures in anti-cancer therapies. Our hypotheses presented here underlie the need for patient-specific multi-target therapies applying the correct ratio of central hits and network influences - in an optimized sequence.

Original languageEnglish
Pages (from-to)262-269
Number of pages8
JournalSeminars in Cancer Biology
Volume23
Issue number4
DOIs
Publication statusPublished - Aug 2013

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Learning
Neoplastic Stem Cells
Neoplasms
Carcinogenesis
Plastics
Therapeutics
Neoplasm Metastasis
Aptitude
Entropy
Pharmaceutical Preparations
Noise

Keywords

  • Adaptation
  • Anti-cancer therapies
  • Cancer attractors
  • Cancer development
  • Epithelial-mesenchymal transition
  • Interactome
  • Networks
  • Signaling

ASJC Scopus subject areas

  • Cancer Research

Cite this

Adaptation and learning of molecular networks as a description of cancer development at the systems-level : Potential use in anti-cancer therapies. / Gyurkó, Dávid M.; Veres, Dániel V.; Módos, Dezsó; Lenti, Katalin; Korcsmáros, T.; Csermely, P.

In: Seminars in Cancer Biology, Vol. 23, No. 4, 08.2013, p. 262-269.

Research output: Contribution to journalArticle

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