Repurposing FDA Drug Compounds against Breast Cancer by Targeting EGFR/HER2

Area of Science:

• Oncology
• Pharmacology
• Computational Chemistry

Background:

• Epidermal growth factor receptor 1 (EGFR) and human epidermal receptor 2 (HER2) are key targets in cancer therapy.
• Drug resistance and varying affinities based on receptor states necessitate novel therapeutic strategies.
• Repurposing existing FDA-approved drugs offers a faster route to new cancer treatments.

Purpose of the Study:

• To identify FDA-approved compounds structurally similar to known EGFR/HER2 inhibitors (lapatinib, gefitinib).
• To computationally evaluate the binding affinity and mechanism of these compounds against EGFR and HER2.
• To assess the in vitro anti-cancer activity of repurposed compounds against breast cancer cell lines.

Main Methods:

• DrugBank analysis for compounds structurally analogous to lapatinib and gefitinib.
• Molecular docking and molecular dynamics (MD) simulations using the MM/GBSA approach.
• In vitro growth inhibition assays on MCF-7 and MDA-MB-23 breast cancer cell lines.

Main Results:

• Identified FDA-approved compounds that bind to the ligand-binding sites of EGFR and HER2.
• Some compounds demonstrated binding that avoided key drug resistance residues.
• In vitro assays confirmed growth inhibitory activity of repurposed compounds against breast cancer cells at micromolar concentrations.

Conclusions:

• Repurposed FDA-approved compounds show potential as novel EGFR and HER2 inhibitors.
• These compounds may offer new therapeutic strategies for cancers driven by EGFR/HER2.
• Computational and in vitro findings support further development of these repurposed drugs for cancer treatment.