Receptor Tyrosine Kinase Dysfunction Related Disease

Receptor Tyrosine Kinase and receptor associated tyrosine kinase are mainly the two-existing type of tyrosine kinase. Three domains are there of receptor tyrosine kinase including are: the outer most extracellular domain, a transmembrane domain and the intracellular domain which has the ability to intrinsically act as a tyrosine kinase.

Receptors tyrosine kinase Receptor and active sites of Phosphorylation 

Structurally 4 similar receptors which come under the family of Epidermal growth factor receptor (EGFR) which is protein kinase. Included are EGFR HER1, HER2, HER3 and HER4 in human beings. Many diseases are linked to EGFR dysregulation.

Cancer is the pathological condition in which the cells are grown abnormally and are undifferentiated with metastatic capabilities. EGFR dysregulation is one the pathophysiological aspect which lead is found in various type of cancers like Lungs cancer, Brain Tumors, esophageal cancer and Intestinal cancer. Dysregulation of EGFR many include overexpression and copy number variation.  

In 40-80 percent Non-small cell lung cancer patient there occur the over expression of EGFR, one of the reasons why this is the potential target for treatment outcomes. EGFR physiologically upon ligand binding go to receptor homo heterodimerization which leads to the activation of cascade of several pathways of downward signaling. These pathways may be Ras-Raf MAP Kinase, STAT and PI3-AKT. The outcomes usually include cell proliferation, apoptosis and cell differentiation.

Abnormal EGFR overexpression is possible to be secondary to changes like 1) Ligand overexpression 2) amplification of the receptor 3) Mutation in the receptor 4) or reduction which occur in the intracellular phosphatases.

Targeted outcomes in such types of cancers in which the EGFR is one of the case for cancer include: Monoclonal antibodies (Mabs) and Receptor tyrosine kinase inhibitors (TKIs).  Mabs (drug i.e transtuzumab, cetuximab and bevacizumab) target the circulation Ligands of receptor tyrosine kinases and prevent their receptor activation.  TKIs (i.e imatinib and gefitinib etc) in the other hand cause the inhibition of kinases of the intracellular domain and prevent ATP to bind to the kinase domain. Drug: Anlotinib Phase 2 clinical Trails (2018). Its mechanism of action is that it is a multitargeted Tyrosine Kinase inhibitor and inhibits multiple sub cascading pathways.