Co-Targeting HER2 and EphB4 Pathways
Final rept. 1 Jul 2011-30 Jun 2013
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
Pagination or Media Count:
Multiple receptor pathways allow for redundancy in growth pathways that are dysregulated in cancer and lead to resistance to targeted therapies. EphB4 angiogenesis receptor can cooperate with HER2 growth factor signaling, and co-targeting HER2 and EphB4 could lead to significant therapeutic benefits. The goal of the full project is to assess the in vitro and in vivo growth and signaling effects of co-targeting using approved anti-HER2 agents, trastuzumab and lapatinib in combination with an agent that inhibits EphB4 signaling developed by our group, a ligand-blocking soluble albumin-stabilized EphB4 peptide termed sEphB4-HSA. The other component of this project Partnering PI submitting this report is to determine the presence of EphB4 and its ligand as well as other angiogenesis mediators and bypass receptors in relationship to response to HER2- targeted therapy and to assess for the enrichment of these markers in pre compared to post treatment tumor tissue. We have confirmed that trastuzumab does improve the pathological response rate in our cohort and have acquired and sectioned all the necessary blocks. We have finalized the titration and validation of all antibodies to be used. In vitro and in vivo studies by the Submitting PI are in progress. These studies together, if supportive of the rationale to co-target EphB4 and HER2 could be readily translated to the clinic as sEphB4-HSA is being tested in a Phase I trial at our institution.
- Anatomy and Physiology
- Medicine and Medical Research