Epidermal growth factor receptor tyrosine kinase inhibitor [Neurosurgery Wiki]

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====== Epidermal growth factor receptor tyrosine kinase inhibitor ======

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A substance that blocks the activity of a [[protein]] called [[epidermal growth factor receptor]] ([[EGFR]]).

A [[tyrosine kinase]] inhibitor (TKI) is a pharmaceutical drug that inhibits [[tyrosine kinase]]s. 

The discovery of [[Epidermal Growth Factor Receptor]] ([[EGFR]])-activating mutations and [[Anaplastic Lymphoma Kinase]] ([[ALK]]) rearrangements in patients with [[non-Small-cell lung cancer]] has allowed for the introduction of small-molecule [[tyrosine kinase inhibitor]]s to the treatment of advanced-stage patients.

EGFR is found on the surface of some normal cells and is involved in cell growth. It may also be found at high levels on some types of cancer cells, which causes these cells to grow and divide. Blocking EGFR may keep cancer cells from growing. Some EGFR inhibitors are used to treat cancer. Also called EGFR [[tyrosine kinase inhibitor]], epidermal growth factor receptor inhibitor, and epidermal growth factor receptor tyrosine kinase inhibitor.

Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia.

They are also called tyrphostins, the short name for “tyrosine phosphorylation inhibitor”, originally coined in a 1988 publication,which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR).

The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphorylate serine or threonine residues and can discriminate between the kinase domains of the EGFR and that of the insulin receptor. It was further shown that in spite of the conservation of the tyrosine-kinase domains one can design and synthesize tyrphostins that discriminate between even closely related protein tyrosine kinases such as EGFR and its close relative HER2.
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Brain-to-tumor interface (BTI) features and volume of peritumoral edema (VPE) were associated with the EGFR mutation status, response to EGFR-TKI and [[T790M]] mutation status in NSCLC patients with BM
((Fan Y, Wang X, Yang C, Chen H, Wang H, Wang X, Hou S, Wang L, Luo Y, Sha X, Yang H, Yu T, Jiang X. Brain-Tumor Interface-Based MRI Radiomics Models to Determine EGFR Mutation, Response to EGFR-TKI and T790M Resistance Mutation in Non-Small Cell Lung Carcinoma Brain Metastasis. J Magn Reson Imaging. 2023 May 5. doi: 10.1002/jmri.28751. Epub ahead of print. PMID: 37144750.)).
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[[EGFR]] and [[ALK]] [[tyrosine kinase inhibitor]]s (TKIs) provide significantly superior systemic response rates and progression-free survival compared to standard chemotherapy in the molecularly defined NSCLC subpopulations. An apparent intracranial activity of new generation TKIs triggered the discussion on their role in brain metastases in lieu of local therapies. The aim of a review of Wrona et al. was to summarize the current therapeutic landscape of [[brain metastases]] management in NSCLC, with a particular focus on EGFR-mutated and ALK-rearranged NSCLC subtypes
((Wrona A, Dziadziuszko R, Jassem J. Management of brain metastases in non-small
cell lung cancer in the era of tyrosine kinase inhibitors. Cancer Treat Rev. 2018
Oct 21;71:59-67. doi: 10.1016/j.ctrv.2018.10.011. [Epub ahead of print] Review.
PubMed PMID: 30366200.
)).
===== Tyrosine kinase inhibitor for non-Small-cell lung cancer intracranial metastases treatment =====
[[Tyrosine kinase inhibitor for non-Small cell lung cancer intracranial metastases treatment]]


====Case reports====
A 57-year-old man presented with seizures. Until the seizure onset, he had been treated for thyroid cancer and its metastases to the thoracic vertebral body with the multi-receptor [[tyrosine kinase inhibitor]] (RTK) [[lenvatinib]] for 4 years. MRI revealed a slightly high intensity lesion in the left frontal base area on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images, and the lesion showed only faint enhancement on T1-weighted images after gadolinium administration. Total resection was performed and the histopathological diagnosis was glioblastoma. However, grade IV histology was observed in only a limited area, and the majority of the specimen showed lower grade histology with moderate vascularization that lacked microvascular proliferation.

Lenvatinib, which is [[antiangiogenic]], might have affected the radiological characteristics, as well as the pathology of the tumor. Brain tumors arising during treatment with RTKs for other cancers could show atypical imaging findings
((Arai N, Sasaki H, Tamura R, Obara K, Yoshida K. Unusual magnetic resonance
imaging findings of a glioblastoma arising during treatment with lenvatinib for
thyroid cancer. World Neurosurg. 2017 Aug 10. pii: S1878-8750(17)31314-1. doi:
10.1016/j.wneu.2017.08.017. [Epub ahead of print] PubMed PMID: 28804045.
)).