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A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
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Multiple Growth Factor Targeting by Engineered Insulin-like Growth Factor Binding Protein-3 Augments EGF Receptor

Elizabeth A Wang1, Wan-Yu Chen2, Chi-Huey Wong3,4

  • 1Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan. wangelizabee@gmail.com.

Scientific Reports
|February 19, 2020
PubMed

Insights

Combination therapy using IGFBP-3-Fc with cancer drugs like erlotinib can overcome treatment resistance by blocking multiple growth factor pathways, potentially extending progression-free survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cancer therapy resistance is a significant challenge due to inherent tumor heterogeneity and continuous evolution.
  • Predicting resistance pathways is difficult, necessitating combination therapies to manage cancer progression.
  • Growth factors are key drivers of cancer resistance, highlighting the need to target multiple pathways simultaneously.

Purpose of the Study:

  • To investigate the potential of simultaneous inhibition of multiple growth factor pathways to enhance precision cancer therapy.
  • To evaluate the efficacy of IGFBP-3-Fc in combination with existing cancer drugs, such as EGFR inhibitors.

Main Methods:

  • Characterization of IGFBP-3 binding affinities to various growth factors (IGF1, IGF2, bFGF, HGF, neuregulin, PDGF AB).
  • Assessment of IGFBP-3-Fc's ability to enhance EGFR inhibitor activity by reducing cell survival and blocking growth factor rescue pathways.
  • In vivo studies evaluating tumor growth inhibition using adjuvant IGFBP-3-Fc with erlotinib compared to erlotinib monotherapy.

Main Results:

  • IGFBP-3 demonstrated nanomolar affinity for multiple growth factors including bFGF, HGF, and PDGF AB, in addition to IGF1 and IGF2.
  • IGFBP-3-Fc enhanced the efficacy of EGFR inhibitors by decreasing cancer cell survival and preventing growth factor-mediated resistance.
  • Combination therapy with IGFBP-3-Fc and erlotinib significantly inhibited tumor growth in vivo and reduced cell survival compared to erlotinib alone.

Conclusions:

  • Simultaneous inhibition of multiple growth factor pathways via IGFBP-3-Fc offers a promising strategy to overcome cancer therapy resistance.
  • This combination approach may improve the efficacy of precision therapies and prolong progression-free survival across various cancer types.
  • Targeting multiple growth factor pathways represents a potential advancement in combating adaptive resistance in cancer treatment.

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