Introduction of Patritumab

Patritumab is a fully human monoclonal antibody developed by scientists collaborating at Amgen and Daiichi Sankyo. It was designed to bind to the receptor tyrosine-protein kinase ERBB3, which is a membrane-bound receptor protein. ERBB3, a member of the epidermal growth factor receptor kinase family (EGF family) that is abnormally activated in several types of cancer. This drug has been used in trials studying the treatment of multiple cancers including head and neck cancer, non-small cell lung cancer and breast cancer. Among these studies, the trials of non-small cell lung cancer and head and neck cancer is in phase Ⅲ and phase Ⅱ respectively, while the trial of breast cancer is at the initial phase Ⅰ.

Mechanism of Action of Patritumab

ERBB3, also known as human epidermal growth factor receptor 3 (HER3), is a member of the human epidermal growth factor kinase family (EGF family), which contains four receptor tyrosine kinases. Interestingly, it exerts biological functions only via forming dimer with other members of the ERBB family because HRBB3 is the kinase-impaired protein required transphosphorylation by its binding partner to be activated. Binding of HRBB3 to its ligand changes its conformation, activating signal transduction on cancer cells through numerous proteins such as phosphoinositide 3-kinase (PI3K), Shc, and E3 ubiquitin ligase neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) and neuregulin receptor degradation protein-1 (Nrdp1). In addition, HRBB3 plays an important role in cell proliferation and survival. Overexpression of HRBB3 has been linked to various primary cancers like breast, ovarian, prostate, colon and pancreas cancers. Furthermore, high expression level of HRBB3 increases cell proliferation in pancreatic adenocarcinoma whereas knock down of HER3 reduces melanoma cell migration and invasion. Oncogenic mutations in HER3 gene were reported in human colon and gastric cancers. Thus, HRBB3 is considered as a therapeutic target in various cancers. Patritumab is designed as a HRBB3 receptor antagonists, which blocks the interaction between HRBB3 and its ligand. Under administration, patritumab binds and inhibits activation to HRBB3, interrupting the transduction of HRBB3-dependent PI3K/Akt signaling and inhibiting the proliferation and differentiation of cancer cells.

Fig.1 Mechanism of action of Patritumab

Table 1. Clinical Projects of Patritumab*

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Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Patrituma

For research use only. Not intended for any clinical use.