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Updated: Jan 17, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Bridging EGFR/TGF-β Signaling to Bypass Resistance to Immune Checkpoint Blockade

Noura J Choudhury1, Aditi Kothari2, Christine M Bestvina1

  • 1Department of Medicine, University of Chicago, Chicago, Illinois.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 23, 2025
PubMed

Insights

Ficerasfusp alfa combined with pembrolizumab shows promise for overcoming resistance to anti-EGFR therapies in squamous cancers. This novel combination targets multiple oncogenic pathways, addressing limitations of current treatments.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Epidermal growth factor receptor (EGFR) is a key target in squamous cell carcinomas.
  • Anti-EGFR monotherapies exhibit limited efficacy due to pathway activation and tumor heterogeneity.
  • Resistance mechanisms necessitate novel therapeutic strategies.

Purpose of the Study:

  • To investigate the potential of ficerafusp alfa in combination with pembrolizumab.
  • To evaluate this combination as a strategy to overcome resistance in squamous cancers.

Main Methods:

  • Early-phase clinical investigation.
  • Utilizing a bifunctional fusion protein (ficerafusp alfa).
  • Combination therapy with pembrolizumab.

Main Results:

  • The combination therapy represents a potential solution for overcoming resistance.
  • Early clinical data suggest efficacy in addressing limitations of monotherapies.

Conclusions:

  • Ficerasfusp alfa and pembrolizumab combination therapy is a promising approach.
  • This strategy may improve outcomes for patients with squamous cancers resistant to anti-EGFR treatments.

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