Systems medicine in colorectal cancer: from a mathematical model toward a new type of clinical trial

Nicoletta Castagnino, Massimo Maffei, Lorenzo Tortolina, Gabriele Zoppoli, Daniela Piras, Alessio Nencioni, Eva Moran, Alberto Ballestrero, Franco Patrone, Silvio Parodi

Research output: Contribution to journalReview articlepeer-review


Current colorectal cancer (CRC) treatment guidelines are primarily based on clinical features, such as cancer stage and grade. However, outcomes may be improved using molecular treatment guidelines. Potentially useful biomarkers include driver mutations and somatically inherited alterations, signaling proteins (their expression levels and (post) translational modifications), mRNAs, micro-RNAs and long noncoding RNAs. Moving to an integrated system is potentially very relevant. To implement such an integrated system: we focus on an important region of the signaling network, immediately above the G1-S restriction point, and discuss the reconstruction of a Molecular Interaction Map and interrogating it with a dynamic mathematical model. Extensive model pretraining achieved satisfactory, validated, performance. The model helps to propose future target combination priorities, and restricts drastically the number of drugs to be finally tested at a cellular, in vivo, and clinical-trial level. Our model allows for the inclusion of the unique molecular profiles of each individual patient's tumor. While existing clinical guidelines are well established, dynamic modeling may be used for future targeted combination therapies, which may progressively become part of clinical practice within the near future. WIREs Syst Biol Med 2016, 8:314–336. doi: 10.1002/wsbm.1342. For further resources related to this article, please visit the WIREs website.

Original languageEnglish
Pages (from-to)314-336
Number of pages23
JournalWiley Interdisciplinary Reviews: Systems Biology and Medicine
Issue number4
Publication statusPublished - Jul 1 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Medicine (miscellaneous)


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