HOW PERJETA® (PERTUZUMAB) IS DESIGNED TO WORK


Proposed mechanism of action of PERJETA

Inhibit HER2 receptor dimerization with PERJETA1

As seen in preclinical models: PERJETA targets a different subdomain on the HER2 receptor than Herceptin does. When used together, PERJETA and Herceptin® (trastuzumab) provide a dual blockade of HER2-driven signaling pathways.1-3

  • The pairing of HER receptors on the cell surface is referred to as dimerization4
  • HER2 dimerizes with the other members of the HER family, including HER1, HER3, and HER4 receptors5
  • HER2:HER3 dimers are believed to be the most oncogenic receptor pairing in HER2+ breast cancer1,6,7
  • This pairing is thought to produce the strongest mitogenic signaling and activate 2 key pathways that regulate cell survival and growth5,8,9:
    • Mitogen-activated protein kinase (MAPK) cell proliferation pathway1,8,9
    • Phosphoinositide 3-kinase (PI3K) cell survival pathway1,10,11

Designed to work with Herceptin for a dual HER2 blockade, based on preclinical studies1

PERJETA binds to subdomain II of HER2 receptors and blocks its ligand-dependent hetrodimerization with HER1, HER3, and HER4.1

PERJETA inhibits HER2:HER3 dimer formation and downstream signaling, suppressing HER2-mediated cell proliferation. It also augments antibody-dependent cell-mediated cytotoxicity (ADCC).1,8-10

Herceptin binds to subdomain IV and disrupts ligand-independent HER2 signaling. Herceptin also mediates ADCC.2,3

PERJETA and Herceptin together provide a dual blockade of HER2-driven signaling pathways.1,2

References