Receptor Tyrosine Kinase-Targeted Cancer Therapy

Abstract

In the past two decades, several molecular targeted inhibitors have been developed and evaluated clinically to improve the survival of patients with cancer. Molecular targeted inhibitors inhibit the activities of pathogenic tyrosine kinases. Particularly, aberrant receptor tyrosine kinase (RTK) activation is a potential therapeutic target. An increased understanding of genetics, cellular biology and structural biology has led to the development of numerous important therapeutics. Pathogenic RTK mutations, deletions, translocations and amplification/over-expressions have been identified and are currently being examined for their roles in cancers. Therapies targeting RTKs are categorized as small-molecule inhibitors and monoclonal antibodies. Studies are underway to explore abnormalities in 20 types of RTK subfamilies in patients with cancer or other diseases. In this review, we describe representative RTKs important for developing cancer therapeutics and predicting or evaluated resistance mechanisms.

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression

“…The EGFR, a transmembrane glycoprotein belonging to the ErbB family of RTKs, is over-expressed in different types of malignant tumours. [6] EGFR amplification and over-expression were found in more than 60% of primary glioblastomas, which leads to excitation of several signalling pathways, including PI3K/Akt and Ras/Raf/MAPK and subsequently proliferation, invasion and survival of tumour cells. [4,[7][8][9][10] Some reports have shown that expression of IRS-1 and IRS-2, two upstream modulators of IGF-1R/Akt pathway, are elevated in various types of cancer cells.…”

“…The epidermal growth factor receptor (EGFR), also known as ErbB‐1, is a transmembrane glycoprotein belongs to the ErbB family of receptor tyrosine kinases (RTKs) that is over‐expressed in different types of human malignancies . Amplification and over‐expression of EGFR gene were found in more than 60% of primary glioblastomas and are believed to be linked to the proliferation, growth, angiogenesis and invasiveness in glioma cells .…”

“…The epidermal growth factor receptor (EGFR), also known as ErbB-1, is a transmembrane glycoprotein belongs to the ErbB family of receptor tyrosine kinases (RTKs) that is over-expressed in different types of human malignancies. [6,7] Amplification and over-expression of EGFR gene were found in more than 60% of primary glioblastomas and are believed to be linked to the proliferation, growth, angiogenesis and invasiveness in glioma cells. [4,8] Ligand-dependent EGFR activation leads to the excitation of two primary downstream signalling pathways: both of PI3-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), which are involved in the proliferation, migration and drug resistance of cancer cells.…”

Ceritinib‐associated hyperglycemia in the Japanese Adverse Drug Event Report Database

“…Targeting of tyrosine kinases is a major cancer therapeutic strategy today. At the same time, unexpected endocrine and metabolic adverse effects of such therapies have been observed, and heightened vigilance is required.…”

“…Genetic alterations in anaplastic lymphoma kinase (ALK), a member of the insulin receptor protein‐tyrosine kinase superfamily, are implicated in the pathogenesis of several human cancers. In non‐small‐cell lung cancer (NSCLC), ALK rearrangement occurs in approximately 3–7% of patients.…”