The role of HER2 in cancer therapy and targeted drug delivery

Abstract

HER2 is highly expressed in a significant proportion of breast cancer, ovarian cancer, and gastric cancer. Since the discovery of its role in tumorigenesis, HER2 has received great attention in cancer research during the past two decades. Successful development of the humanized monoclonal anti-HER2 antibody (Trastuzumab) for the treatment of breast cancer further spurred scientists to develop various HER2 specific antibodies, dimerization inhibitors and kinase inhibitors for cancer therapy. On the other hand, the high expression of HER2 and the accessibility of its extracellular domain make HER2 an ideal target for the targeted delivery of anti-tumor drugs as well as imaging agents. Although there is no natural ligand for HER2, various artificial ligands targeting HER2 have been developed and applied in various targeted drug delivery systems. The emphasis of this review is to elucidate the roles of HER2 in cancer therapy and targeted drug delivery. The structure and signal pathway of HER2 will be briefly described. The role of HER2 in tumorigenesis and its relationship with other tumor markers will be discussed. For the HER2 targeted cancer therapy, numerous strategies including the blockage of receptor dimerization, inhibition of the tyrosine kinase activity, and interruption of the downstream signal pathway will be summarized. For the targeted drug delivery to HER2 positive tumor cells, various targeting ligands and their delivery systems will be described in details.

A study of the incidence and prognostic value of HER-2 overexpression in patients with gastric adenocarcinoma in Odisha

“…Herceptin (trastuzumab) is a recombinant human monoclonal antibody designed to target and block the function of HER2 by directly binding to the extracellular domain of the receptor [22,23]. It has been used for the treatment of HER2 overexpressing breast cancer for more than 10 years and was approved by the European Medicines Agency [24] in 2010 for use in combination with capecitabine or 5-FU and cisplatin for metastatic gastric or GE junction cancers, based on data from the 'ToGA'' clinical trial.…”

Using Clinical Proteomics to Discover Novel Anti-Cancer Targets for MAb Therapeutics

“…The resulting antibody named tratsuzumab was a humanized mouse monoclonal antibody and was later approved by the FDA in 1998 for treatment of metastatic breast cancer (Slamon, Leyland-Jones et al 2001). Tratsuzumab binds to a site close to the transmembrane region which is out with the potential ligand docking site effecting dimerization with other Her family members (Tai, Mahato et al 2010). It was an instant success when used along side conventional chemotherapeutic agents with recurrence rates halved and mortality dropping by 30% which was seen to far out weigh the small risk of cardiotoxicity sometimes seen (Chang 2007).…”

Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells in�vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

“…Human epithelial growth factor receptor 2 (HER2) is over-expressed in a significant proportion of gastric cancers (6-23%) (8). It is associated with tumor invasion, metastasis, chemoresistance and poor prognosis (9).…”