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INTERNATIONAL CONGRESS OF

CancerGenetics

• Dual Targeting of CD73/EGFR Axis via siRNA Nanocarriers: A Novel Immunotherapeutic Strategy Against Breast Cancer

• Keivan Ardeshiri ,¹ Hadi Hassannia,² Ghasem Ghalamfarsa,³ Hanieh Jafary ,⁴ Farhad Jadidi,^5,*
  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
  2. Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
  3. Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
  4. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
  5. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  
  
  
• Introduction: Targeting synergistic pathways in the tumor microenvironment (TME) is crucial for effective cancer immunotherapy. The CD73 and EGFR axes cooperatively promote tumor growth, immune suppression, and drug resistance. We hypothesized that simultaneous blockade of both pathways using siRNA nanocarriers could enhance therapeutic efficacy in aggressive breast cancer.
• Methods: We employed previously developed nanocarriers to deliver anti-CD73 and anti-EGFR siRNAs to murine 4T1 breast cancer cells. Cell viability was assessed via MTT assay, while migration and proliferation were evaluated using scratch and colony formation assays. Therapeutic efficacy was further validated in an in ovo tumor model (chick chorioallantoic membrane).
• Results: Dual siRNA treatment significantly induced cancer cell death compared to single-target or control groups. Combined CD73/EGFR silencing reduced cancer cell migration and proliferation. In the in ovo model, dual therapy decreased tumor volume versus untreated controls.
• Conclusion: Our results show that coordinated CD73/EGFR inhibition disrupts their reciprocal expression and function, leading to potent antitumor effects. This nanocarrier-based strategy presents a promising immunotherapeutic approach for breast cancer, warranting further investigation in advanced preclinical models.
• Keywords: 4T1 CD73 EGFR breast cancer cancer therapy