Pertuzumab in gastrointestinal cancer

Human epidermal growth factor receptor 2 (HER2) and HER3 are altered in multiple tumor types, including gastrointestinal cancer. The HER2/HER3 dimer is crucial for HER2-mediated signaling in HER2-positive tumors. HER2-targeting agents, including trastuzumab, lapatinib, trastuzumab emtansine, and pertuzumab, have been approved for the treatment of HER2-positive breast cancer, with trastuzumab also approved for the treatment of HER2-positive gastric cancer. Pertuzumab, a recombinant humanized immunoglobulin (Ig) G1 monoclonal antibody targeting HER-2, binds to the dimerization domain (extracellular domain II) of HER2, which leads to blocking of ligand-induced HER2 heterodimerization. It is under investigation in gastrointestinal cancers, including HER2-positive gastric cancer.

In this review, the authors summarize the biology of HER2/HER3 and its alterations in gastrointestinal cancers. The authors focus specifically on the current status of development of pertuzumab in gastrointestinal cancers.

The HER2/HER3 alteration in gastrointestinal cancers is quite interesting. In HER2-positive gastric cancer, the dual blockade of HER2 and HER3 using trastuzumab and pertuzumab is being tested in an international phase III trial, the JACOB study. This strategy may benefit HER2-positive gastric cancer patients more as in the case of HER2-positive breast cancer. In other gastrointestinal cancers, including biliary tract cancer, esophageal cancer, pancreatic cancer, and colorectal cancer, there is huge room for the development of pertuzumab.