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Πέμπτη 30 Μαΐου 2019

Mutations that lead to EGFR overexpression (known as upregulation or amplification) have been associated with a number of cancers, including adenocarcinoma of the lung (40% of cases), anal cancers,[16] glioblastoma (50%) and epithelian tumors of the head and neck (80-100%).[17] These somatic mutations involving EGFR lead to its constant activation, which produces uncontrolled cell division.[18] In glioblastoma a specific mutation of EGFR, called EGFRvIII, is often observed.[19] Mutations, amplifications or misregulations of EGFR or family members are implicated in about 30% of all epithelial cancers.The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.[5] The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer.[6] Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors. Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either by blocking EGFR binding sites on the extracellular domain of the receptor or by inhibiting intracellular tyrosine kinase activity, can prevent the growth of EGFR-expressing tumours and improve the patient's condition.

Biomarkers

Molecular markers used to guide treatment, assess prognosis, or detect relapse.

EGFR

In the JAMA study, researchers confirmed the previously known clinical and genomic features of NSCLC patients in their large clinico-genomics database.
Based on the findings, MD Anderson is already using HER2 status to recommend patients for clinical trials instead of EGFR drugs and authors recommend others follow suit.
The researchers believe using cerebral spinal fluid will enable them to identify brain tumors with a higher sensitivity than with blood samples.
Qiagen's test detects the most frequently occurring somatic mutations in EGFR in less than four hours using real-time PCR on the Rotor-Gene Q platform.
The firms will begin a prospective lung cancer study using Biocartis' Idylla EGFR mutation test in European countries, including Belgium, France, Germany, and Italy.
Researchers separately found that the assay had high concordance with other techniques in cancers including colorectal and endometrial carcinomas.
The assay can identify KRAS, NRAS, PIK3CA, BRAF, and EGFR gene mutations, as well as 19 gene rearrangements of the ALK, ROS1, RET, NTRK1, and MET genes from FFPE.
During the meeting, researchers presented studies on combination immunotherapies and the efficacy of giving molecularly-informed treatments earlier in the disease continuum.
The new approval will allow the use of Qiagen's Therascreen EGFR RGQ PCR Kit as a companion diagnostic for Pfizer's Vizimpro in NSCLC patients.
The approval includes the use of either tumor tissue or plasma and follows previous approvals with Genentech's Tarceva (erlotinib) and AstraZeneca's Tagrisso (osimertinib).

EGFR

Genome and RNA sequencing led to recurrent EGFR and BRAF rearrangements in cryptogenic congenital mesoblastic nephroma and infantile fibrosarcoma soft tumors.
The FDA approved its use with tissue or plasma biopsies, giving clinicians a non-invasive option to conduct a test that provides results in a day.
The company has highlighted the study as evidence that its test would outperform Roche's FDA-approved liquid biopsy assay if implemented in the clinic.
An extended labeling claim has added detection of three additional EGFR mutations to help ID NSCLC patients for whom Boehringer Ingelheim's Gilotrif is indicated.
The researchers found that most advanced EGFR-mutant lung cancer patients harbored changes in an average of two to three other oncogenes.
The changes include recommendations for first line immunotherapy in patients with high PD-L1 expression, and clarification on use of targeted therapies.
The so-called universal CDx approved by the FDA can gauge alterations across multiple genes associated with response to three lung cancer treatments. 
Clinicians say they are using blood-based tests for patients who can't be biopsied as a way to get test results sooner, but implementing tests smartly and appropriately remains a challenge.
In head-to-head studies, a next-generation EGFR inhibitor and an ALK inhibitor beat their older counterparts in staving of cancer progression.  
Results from a recent study clarify some conflicting prior determinations, and provide a new rationale to further explore the FCGR2A biomarker in prospective trials.

EGFR

Genentech's Alecensa and AstraZeneca's Tegrisso are the latest precision lung cancer drugs, and Xalkori might soon be an option for a new molecular subpopulation.
Non-small cell lung cancer patients with EGFR mutations now have three treatment choices, and AstraZeneca is working on newer personalized treatment options.

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