Understanding Perjeta & Perjeta with Herceptin
 

Inhibit Dimerization for More Comprehensive HER2 Blockade

HER2 dimerization inhibition with PERJETA¹

• The pairing of HER receptors on the cell surface is referred to as dimerization²
• HER2 dimerizes with the other members of the HER family, including HER1, HER3, and HER4³
• HER2:HER3 dimerization is believed to produce the strongest mitogenic signaling and activate 2 key pathways that regulate cell survival and growth^3-5
  • Mitogen-activated protein kinase (MAPK) pathway^1,4,5
  • Phosphoinositide 3-kinase (PI3K) pathway^1,6,7

http://www.perjeta.com/hcp/images/hc...merization.jpg

Proposed mechanism of action of PERJETA with Herceptin video

The video below shows the proposed mechanism of action of PERJETA in combination with Herceptin. When used together, the combination provides a more comprehensive blockade of HER2-driven signaling pathways.¹
Note: This video contains sound, so please adjust the volume.
http://www.perjeta.com/hcp/images/hc...load-video.pngAs seen in preclinical models:

PERJETA targets a different domain on the HER2 receptor than Herceptin (trastuzumab), allowing the combination to provide a more comprehensive blockade of HER2-driven signaling pathways.^1,8,9


Proposed mechanism of action of PERJETA with Herceptin

1.


http://www.perjeta.com/hcp/images/hcp/moa/step-1.jpg

PERJETA binds to subdomain II and blocks ligand‑dependent HER2 heterodimerization with HER1, HER3, and HER4.¹


2.


http://www.perjeta.com/hcp/images/hcp/moa/step-2.jpg

PERJETA inhibits HER2:HER3 dimer formation and downstream signaling, while also mediating antibody‑dependent cell-mediated cytotoxicity (ADCC).^1,4-6


3.


http://www.perjeta.com/hcp/images/hcp/moa/step-3.jpg

Herceptin binds to subdomain IV and disrupts ligand‑independent HER2 signaling. Herceptin also mediates ADCC.^8,9


4.


http://www.perjeta.com/hcp/images/hcp/moa/step-4.jpg

PERJETA + Herceptin provide a more comprehensive blockade of HER2-driven signaling pathways.<sup>1,8

http://www.perjeta.com/hcp/moa;jsess...677.gxe501b-m1
</sup>