The epidermal growth factor receptor (EGFR is a tumor resistance biomarker which plays an essential role in the differentiation and proliferation upon activation through the binding of one of its ligands. A non-ligand-binding member of EGFR family, HER2 exerts its activity through heterodimerisation along with its other family members. HER2 is a transmembrane growth factor receptor present in the normal and malignant breast epithelial cells. The phosphorylation of the intracellular tyrosine kinase activates intracellular signaling, thereby, leading to the activation of genes responsible for cellular growth.
The functional activation of HER2 promotes oncogenesis, which further leads to the investigation of HER2-directed agents in cancers with HER2 alterations. This has been best characterized in the context of HER2 gene amplification in breast and gastric / gastro-oesophageal junction carcinomas, for which several HER2-directed drugs have become a part of standard treatment regimens. It has been found that 15-30% of breast cancers and 10-30% of gastric / gastroesophageal cancers have reported amplification or overexpression of HER2. These carcinomas are known as HER2-positive. HER2 biomarker have potentially emerged as a novel predictive biomarker for HER2-directed therapies. Further, preclinical data suggests that activating HER2 mutations are potent oncogenic drivers in a manner analogous to HER2 gene amplification and such mutations may confer sensitivity to HER2-directed drugs in a similar manner.
The anti-HER2 therapies target the HER2 receptor proteins present on the surface of tumor cells, inhibiting the HER2 receptors from receiving signals in order to terminate the cellular growth. These therapies can be used as a monotherapy or in combination with other therapeutic modalities, such as chemotherapy, surgery or radiation therapy.
The HER2 mutation results in oncogenic transformation of the breast epithelial cells. As the HER2 gene amplification, or protein overexpression is regarded as the basic mechanism of HER2-driven oncogenesis, it can potentially be used as a main predictive biomarker for the identification of patients, likely to be benefitted from anti-HER2 therapies. Considering this, there are several drugs targeting the deregulation of HER2, including monoclonal antibodies, ADCs, and small molecule TKIs (tyrosine kinase inhibitors), approved by the US Food and Drug Administration (FDA).
The Evolving landscape of HER2 Targeting Therapies
Even though efforts for development of HER2 targeting therapies have been undertaken by players based all across the globe, majority of the developers are headquartered in North America. Within North America, US has emerged as a prominent region where maximum product developers are located. This is followed by players based in Asia Pacific; within this region, majority of the developers are headquartered in China. Further, many players are located in Europe as well. Further, as more product candidates are approved by regulatory authorities across the globe, the number of clinical trials across different regions is anticipated to increase. To get a detailed information on the key players, recent developments, and the likely market evolution, visit this link
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