How does camptothecin interact with the EGFR receptor in breast cancer?

In addition to HER2, the epidermal growth factor receptor (EGFR) is another key receptor implicated in breast cancer progression. Understanding camptothecin's interaction with EGFR is crucial for evaluating its potential as a dual-targeting agent for breast cancer.

Camptothecin exhibits a binding energy of −6.00 kcal/mol and a dissociation constant (Kd) of 40.01 µM with EGFR, which is less favorable compared to its interaction with HER2. The interactions between camptothecin and EGFR are primarily mediated by hydrogen bonds, particularly with Tyrosine 830, and hydrophobic interactions involving Leucine 694, Leucine 820, and Valine 702. While these interactions stabilize the camptothecin-EGFR complex, the overall binding affinity is weaker than that observed with HER2, suggesting that camptothecin may have a higher selectivity for HER2. This differential binding behavior indicates that camptothecin could potentially offer a targeted approach to treat HER2-positive breast cancer while minimizing off-target effects on EGFR.