Abstract
Human epidermal growth factor receptor (HER) 2 (HER2) is overexpressed in 20–30% of breast cancers. HER2 is a preferred target for treating HER2-positive breast cancer. Trastuzumab and pertuzumab are two HER2-targeted monoclonal antibodies approved by the Food and Drug Administration (FDA) to use as adjuvant therapy in combination with docetaxel to treat metastatic HER2-positive breast cancer. Adding the monoclonal antibodies to treatment regimen has changed the paradigm for treatment of HER2-positive breast cancer. Despite improving outcomes, the percentage of the patients who benefit from the treatment is still low. Continued research and development of novel agents and strategies of drug combinations is needed. A thorough understanding of the molecular mechanisms underlying the action and synergism of trastuzumab and pertuzumab is essential for moving forward to achieve high efficacy in treating HER2-positive breast cancer. This review examined and analyzed findings and hypotheses regarding the action and synergism of trastuzumab and pertuzumab and proposed a model of synergism based on available information.
Highlights
There are four members in the Human epidermal growth factor receptor (HER) receptor family
Its recent approval by the Food and Drug Administration (FDA) to be used in combination with trastuzumab and docetaxel has significantly improved the outcome of the patients with metastatic HER2-positive breast cancer [11,19,23,24,25]
As HER2/HER3 heterodimer-mediated activation of PI3K-Akt-mTor has been considered the most important signaling pathway driving the development of breast cancer, and constitutive activation of this pathway identified as a major resistant mechanisms for trastuzumab resistance, combined inhibition of both HER2 and PI3K-Akt-mTor has been explored to overcome trastuzumab resistance [165,166]
Summary
There are four members in the HER receptor family. They are epidermal growth factor (EGF). Acquired trastuzumab resistance has developed with time, which needs to be overcome [19,21,22] Its recent approval by the FDA to be used in combination with trastuzumab and docetaxel has significantly improved the outcome of the patients with metastatic HER2-positive breast cancer [11,19,23,24,25]. The lack of a good understanding of the mechanisms underlying the action and synergism of trastuzumab and pertuzumab severely limit its application and efficacy. Despite these achievements, the persisting high toll of deaths necessitates newer therapies and combinations [27]. We will focus on the reported mechanisms and hypotheses underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
