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Mapping oncogenic protein interactions for precision medicine.

Mehdi Sharifi Tabar1,2,3, Habib Francis1,2,3, Dannel Yeo3,4,5

  • 1Gene & Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.

International Journal of Cancer
|February 3, 2022
PubMed
Summary

Cancer disrupts normal protein-protein interactions (PPIs), creating oncogenic PPIs (oncoPPIs). This study proposes a workflow to map these oncoPPIs, crucial for developing new cancer drugs and precision medicine approaches.

Keywords:
cancerdrug discoverygenomic alterationprecision medicineprotein-protein interaction

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Normal protein-protein interactions (normPPIs) are vital for physiological regulation.
  • Cancer involves disrupted, hijacked, or reprogrammed protein-protein interactions, forming oncogenic PPIs (oncoPPIs).
  • Genomic alterations can drive oncoPPIs, a hallmark of many cancers.

Purpose of the Study:

  • To address the lack of comprehensive reference maps for cancer-specific oncoPPIs.
  • To discuss challenges in characterizing oncoPPIs.
  • To propose a multidisciplinary workflow for identifying and characterizing oncoPPIs.

Main Methods:

  • Leveraging advances in mass spectrometry (MS)-based interactomics.
  • Utilizing structural biology techniques.
  • Employing drug discovery methodologies.

Main Results:

  • Identification of key hurdles in characterizing oncoPPIs.
  • Proposal of a three-phase multidisciplinary workflow to overcome these challenges.
  • Establishment of a framework for systematic oncoPPI identification.

Conclusions:

  • Systematic mapping of cancer-specific oncoPPIs is urgently needed.
  • The proposed workflow can facilitate the creation of comprehensive oncoPPI reference maps.
  • Identifying oncoPPIs will drive novel drug discovery and advance precision medicine.