Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and

Hande Beklen1, Sema Arslan2, Gizem Gulfidan1

  • 1Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.

Insights

This study identifies novel biomarkers and drug candidates for colorectal cancer (CRC) treatment using a novel interactome-based drug repositioning strategy. Several drugs showed significant in vitro efficacy, offering new therapeutic avenues for CRC.

Area of Science:

  • Oncology
  • Bioinformatics
  • Pharmacology

Background:

  • Colorectal cancer (CRC) necessitates innovative treatment strategies.
  • Identifying reliable biomarkers and effective drug candidates is crucial for improving CRC patient outcomes.

Purpose of the Study:

  • To propose novel biomarkers and drug candidates for colorectal cancer (CRC) treatment.
  • To utilize differential interactome-based drug repositioning for identifying therapeutic targets and drugs.

Main Methods:

  • Identification of differentially interacting proteins and modules with prognostic value using survival analyses.
  • Drug repositioning targeting significant proteins, followed by in silico molecular docking.
  • In vitro validation of candidate drugs using colorectal cancer (CRC) cell lines.

Main Results:

  • Six key modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were identified for their prognostic significance.
  • Eight potential drugs were repositioned, including abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone.
  • Significant in vitro inhibition was observed for abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline in CRC cell lines.

Conclusions:

  • The study presents a novel approach for colorectal cancer (CRC) treatment strategy development.
  • Identified biomarkers and repositioned drugs offer potential complementary therapeutic options for CRC.

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