Synergy between trastuzumab and pertuzumab for human epidermal growth factor 2 (Her2) from colocalization: an in silico based mechanism.

ABSTRACT:

Introduction

Human epidermal growth factor 2 (Her2), a receptor tyrosine kinase, is overexpressed in breast cancers. It has been successfully targeted by small molecule kinase inhibitors and by antibodies. Recent clinical data show a synergistic response in patients when two antibodies, trastuzumab and pertuzumab, are given in combination.

Methods

This unexpected effect is rationalized through computer models and molecular dynamic simulations by hypothesizing that the two antibodies can co-localize on the same molecule of the Her2 extracellular domain.

Results

Simulations suggest that the clinical synergism observed for the two antibodies arises partly from enhanced affinity that originates in cooperative interactions between these two antibodies when they are co-loca

SUBMITTER: Fuentes G 

PROVIDER: S-EPMC3218942 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature