• Genetic alterations that lead to de-regulation of the autocrine Wnt pathway result in transactivation of epidermal growth factor receptor (EGFR) and other pathways, in turn contributing to proliferation of tumor cells. (wikipedia.org)
  • OCEA ) announced today that its cancer-targeting immunotherapy antibody candidate has demonstrated effective tumor reduction against an aggressive subset of Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutations. (yahoo.com)
  • Tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (EGFR) are now standard treatment in the clinic for patients with advanced EGFR mutant non-small-cell lung cancer (NSCLC). (researchgate.net)
  • The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. (bmj.com)
  • Alterations in receptor tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1, include overexpression, amplification or mutations. (bmj.com)
  • Novel therapeutic agents, in particular those that specifically target members of the human epidermal growth factor receptor (HER (ErbB1)) pathway, have shown encouraging therapeutic efficacy. (bmj.com)
  • Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. (aacrjournals.org)
  • The epidermal growth factor receptor (EGFR) is frequently overexpressed in the most common malignant glioma, glioblastoma (GBM), and represents an important therapeutic target. (oncotarget.com)
  • Epidermal growth factor receptor (EGFR) inhibition with erlotinib reduces hypoxia in vivo. (precisionimaging.center)
  • Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. (biomedcentral.com)
  • [ 6 ] A majority of these tumors will exhibit polysomy of the epidermal growth factor receptor ( EGFR ) genetic locus on chromosome 7 in subsets of tumor cells. (medscape.com)
  • Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer. (cdc.gov)
  • BACKGROUND: RAS mutations are the only validated biomarkers in metastatic colorectal cancer (mCRC) for anti-epidermal growth factor receptor (EGFR) therapy. (bvsalud.org)
  • The model showed that the well-known cancer gene, EGFR ( epidermal growth factor receptor ) can alone initiate the brain tumors to grow in mice, resulting in tumors that were highly representative of human glioblastomas. (medicalxpress.com)
  • Compound epidermal growth factor receptor ( EGFR ) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). (biomedcentral.com)
  • CO-1686 is a novel, oral, targeted covalent (irreversible) inhibitor of the cancer-causing mutant forms of epidermal growth factor receptor (EGFR) currently being studied for the treatment of non-small cell lung cancer (NSCLC). (adooq.com)
  • BMS-690514 is a potent and selective inhibitor of epidermal growth factor receptor (EGFR), HER2, and HER4, as well as the VEGF receptor kinases. (adooq.com)
  • Erlotinib hydrochloride is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). (adooq.com)
  • BIBW2992 (Afatinib) is tyrosine kinase inhibitor (TKI) that irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. (adooq.com)
  • Mice lacking the epidermal growth factor receptor (EGFR) develop epithelial defects and a neurodegenerative disease and die within the first month of birth. (silverchair.com)
  • This device is a real-time PCR test for the qualitative detection of exon 19 deletions and exon 21 (L858R) substitution mutations of the epidermal growth factor receptor (EGFR) gene in DNA derived from formalin-fixed paraffin-embedded (FFPET) human non-small cell lung cancer (NSCLC) tumor tissue. (pdffox.com)
  • BDTX-1535, a fourth-generation, brain-penetrant epidermal growth factor receptor (EGFR) MasterKey tyrosine kinase inhibitor (TKI), is under investigation for the treatment of NSCLC harboring intrinsic driver and/or acquired resistance (post-osimertinib) EGFR mutations and glioblastoma multiforme (GBM) with multiple EGFR alterations. (drug-dev.com)
  • This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. (biomedcentral.com)
  • These observations spurred better cancer patients characterization particularly at the level of cancer markers such as the epidermal growth factor receptor (EGFR). (biomedcentral.com)
  • However, patients who develop resistance to TKI treatment often acquire a somatic resistance mutation (T790M) located in the catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. (bcm.edu)
  • De-regulation of the autocrine Wnt signaling pathway via mutations in APC and Axin have been linked to activation of various types of human cancer. (wikipedia.org)
  • The studies demonstrate the ability of Ocean Biomedical's cancer-targeting immunotherapeutic antibody to control the growth of human tumor cells with EGFR mutations by suppressing CHI3L1 activity. (yahoo.com)
  • First-generation EGFR TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, have resulted in a significant improvement in outcome for NSCLC patients with activating EGFR mutations (L858R and Del19). (researchgate.net)
  • The second-generation EGFR/HER TKIs were developed to treat resistant disease, targeting not only T790M but EGFR-activating mutations and wild-type EGFR. (researchgate.net)
  • The third-generation EGFR TKIs selectively and irreversibly target EGFR T790M and activating EGFR mutations, showing promising efficacy in NSCLC resistant to the first- and second-generation EGFR TKIs. (researchgate.net)
  • Currently, the first-generation gefitinib and erlotinib and second-generation afatinib have been approved for first-line treatment of metastatic NSCLC with activating EGFR mutations. (researchgate.net)
  • In this review, we summarize the available post-progression therapies including third-generation EGFR inhibitors and combination treatment strategies for treating patients with NSCLC harboring EGFR mutations and address the known mechanisms of resistance. (researchgate.net)
  • Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. (bmj.com)
  • A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identify EGFR mutations, each of which has advantages and disadvantages. (bmj.com)
  • However, 25% to 30% of patients with EGFR -activating mutations show intrinsic resistance, and the responders invariably acquire resistance to gefitinib. (aacrjournals.org)
  • Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR -activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. (aacrjournals.org)
  • Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. (cdc.gov)
  • Safety, tolerability, pharmacokinetics, and preliminary efficacy of YK-029A in treatment-naïve patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations: A phase I trial. (cdc.gov)
  • Germline mutations and developmental mosaicism underlying EGFR -mutant lung cancer. (cdc.gov)
  • Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer. (cdc.gov)
  • Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations. (cdc.gov)
  • this group included all patients in dose escalation and in dose expansion Cohort 1 (i.e., pretreated patients with adenocarcinoma histology and EGFR mutations) [4]. (memoinoncology.com)
  • Forty of the 57 patients in the efficacy population had detectable EGFR exon 19 deletions or L858R mutations in plasma at baseline. (memoinoncology.com)
  • In patients who have developed disease progression on treatment with the third-generation TKI osimertinib, resistance mutations are most commonly either EGFR-dependent (e.g. (memoinoncology.com)
  • Both agents have shown clinical activity across various EGFR mutations [7-11]. (memoinoncology.com)
  • Based on these observations, 45 chemotherapy-naïve patients with EGFR exon 19 deletions or L858R mutations who had progressed on osimertinib were treated with amivantamab plus lazertinib in the dose-expansion phase of the phase I CHRYSALIS trial. (memoinoncology.com)
  • To identify which genes help EGFR to drive the cancer, the team used the PiggyBac transposon technique-a small section of DNA inserted into different parts of the genome to introduce mutations. (medicalxpress.com)
  • This revealed more than 200 known and novel mutations in tumor suppressor genes that were working with EGFR to drive brain tumor growth, many of which present new drug targets. (medicalxpress.com)
  • The team compared the results with human genome sequences from glioblastoma patients and uncovered many genetic mutations found in both humans and mice. (medicalxpress.com)
  • Human genomic data contains many mutations implicated in glioblastoma, without clear indication of which specific mutations drive the cancer. (medicalxpress.com)
  • However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. (biomedcentral.com)
  • We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). (biomedcentral.com)
  • Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. (biomedcentral.com)
  • Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments. (biomedcentral.com)
  • Short in-frame deletions in exon 19 (19-Del) and point mutations in EGFR exon 21 p.L858R are the most common activating mutations in EGFR , accounting for approximately 90% of all EGFR mutations in NSCLC [ 5 , 6 ]. (biomedcentral.com)
  • Besides 19-Del and EGFR exon 21 p.L858R, extensive research has uncovered a wide array of rare EGFR activating or resistant mutations in NSCLC, including EGFR exon 18 p.G719X, EGFR exon 20 p.S768I, EGFR exon 21 p.L861Q, EGFR exon 20 p.T790M, and EGFR exon 20 insertions (20ins). (biomedcentral.com)
  • Drug repurposing has been hotly pursued by many groups, and here the authors took 183 small molecules, including 12 FDA-approved drugs, and screened them against a panel of 76 mutant kinases (covering 21 wild-type kinases), where all but 8 of the mutations have been implicated in a human disorder. (genengnews.com)
  • 2. The cobas® EGFR Mutation Test v2 kit provides reagents for automated real-time PCR amplification and detection of the EGFR mutations. (pdffox.com)
  • The BDTX-1535 expansion cohort portion of the study will assess single-agent objective response rate (ORR) in a second- or third-line setting in NSCLC patients with EGFR intrinsic driver and/or acquired resistance mutations, who have received prior treatment with approved EGFR TKI. (drug-dev.com)
  • The dosing of the first patients in the expansion cohorts follows the company's initial data readout from the dose escalation portion of the BDTX-1535 Phase 1 clinical study, which demonstrated clinical proof of activity through radiographic responses in NSCLC patients harboring diverse types of EGFR mutations including intrinsic driver and post-osimertinib acquired resistance EGFR mutations. (drug-dev.com)
  • The Phase 1 expansion cohorts will assess objective response rate and durability of response in NSCLC patients whose disease has progressed after prior EGFR inhibitor therapy, including prior osimertinib, and who have evidence of a variety of EGFR driver or resistance mutations that are targeted by BDTX-1535," said Sergey Yurasov, MD, PhD, Chief Medical Officer of Black Diamond Therapeutics. (drug-dev.com)
  • BDTX-1535 was designed to disrupt the limited existing treatment paradigm by addressing real-world patterns of patient-specific EGFR mutations, and we remain focused on the rapid advancement of this novel MasterKey inhibitor. (drug-dev.com)
  • Emergence of intrinsic driver and acquired resistance EGFR mutations to osimertinib represents a significant unmet need for patients with EGFR-mutant lung cancer. (drug-dev.com)
  • Thirteen percent of patients in the US with EGFR mutation-positive NSCLC show presence of intrinsic driver mutations, which are associated with worse clinical outcomes when treated with currently approved EGFR TKIs. (drug-dev.com)
  • Fifteen percent of patients in the US whose disease has progressed after osimertinib therapy show evidence of acquired resistance EGFR mutations (eg, C797S) for which currently there is no approved EGFR TKI. (drug-dev.com)
  • The company is advancing BDTX-1535 as a potential targeted therapy option for patients with this broad spectrum of EGFR mutations in second-line NSCLC, and plans to investigate safety and efficacy in a first-line setting in NSCLC patients with intrinsic driver EGFR mutations after discussion with the US FDA. (drug-dev.com)
  • The trial is evaluating BDTX-1535 in patients with advanced/metastatic NSCLC harboring EGFR mutations with or without central nervous system (CNS) disease, or with recurrent GBM expressing EGFR alterations. (drug-dev.com)
  • Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (− ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor's function and promote tumorigenesis. (biomedcentral.com)
  • A combination of in vitro and in vivo models with validation in human tumors has identified AXL activation as a new mechanism of acquired resistance to EGFR inhibitors in non-small cell lung cancer. (nature.com)
  • Trever Bivona and colleagues identify the upregulation of the AXL kinase in human non-small cell lung cancer with acquired resistance to erlotinib. (nature.com)
  • The authors suggest AXL as a potential therapeutic target that may prevent or overcome acquired resistance in patients with EGFR -mutant lung cancer. (nature.com)
  • Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. (cdc.gov)
  • CONCLUSIONS: AXL is a marker of poor prognosis in mCRC with consistent clinical and preclinical evidences of involvement in primary and acquired resistance to anti-EGFR drugs in RAS WT patients. (bvsalud.org)
  • The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. (rcsb.org)
  • In past 2 years, Femtopath help Abcam-Epitomics to develop a new EGFR L858R specific antibody. (femtopath.com)
  • Due to the challenging nature of developing mutation specific antibodies, only a few EGFR L858R monoclonal antibodies exist for immunohistochemical (IHC) testing. (femtopath.com)
  • Here we report a new EGFR L858R RabMAb developed by utilizing the RabMAb ® technology, designated as clone EP344. (femtopath.com)
  • The concordance of the IHC staining results with EGFR L858R mutation status was analyzed. (femtopath.com)
  • Rabbits were immunized with EGFR L858R peptide. (femtopath.com)
  • Antibody from final hybridoma cell line was further characterized by extensive IHC testing using formalin fixed paraffin embedded (FFPE) human normal, tumor and EGFR L858R mutant tumor tissues. (femtopath.com)
  • EGFR L858R gene mutation was detected by FemtoPath (Patent No. P2708-TW) or Sanger dideoxy sequencing (ABI 3730) mutation analysis. (femtopath.com)
  • The concordance of EP344 IHC staining results with mutation status was analyzed and compared against EGFR L858R rabbit monoclones SP125 and 43B2. (femtopath.com)
  • A 175 KDa EGFR L858R protein was detected by WB in EGFR L858R mutant H1975 cells, but not in wild type cells. (femtopath.com)
  • Furthermore, a separate group of 13 lung carcinomas with EGFR L858R mutation was stained with all antibodies. (femtopath.com)
  • RabMAbs anti-EGFR L858R, clone EP344 is specific and sensitive in the detection of target mutant proteins by IHC in FFPE tissues. (femtopath.com)
  • EP344 is highly concordant with EGFR L858R mutation status. (femtopath.com)
  • Comparing to current EGFR L858R antibodies, EP344 may be a potentially better tool for predicting EGFR L858R mutation status by IHC testing. (femtopath.com)
  • However, after a median duration of response of ~12 months, all patients develop tumor resistance, and in over half of these patients this is due to the emergence of the EGFR T790M resistance mutation. (researchgate.net)
  • Although they exhibited promising anti-T790M activity in the laboratory, their clinical activity among T790M+ NSCLC was poor mainly because of dose-limiting toxicity due to simultaneous inhibition of wild-type EGFR. (researchgate.net)
  • Among the third-generation EGFR TKIs, osimertinib is today the only drug approved by the Food and Drug Administration and the European Medicines Agency to treat metastatic EGFR T790M NSCLC patients who have progressed on or after EGFR TKI therapy. (researchgate.net)
  • In Part A of the study, dose escalation is carried out where MTD is evaluated using Bayesian Optimal Interval (BOIN) design in subjects with advanced NSCLC harboring EGFR-mutation of C797S or T790M. (uci.edu)
  • In Part B, dose exploration is carried out to further evaluate the safety of JIN-A02 and to determine the RP2D using 2 preliminary effective dose levels and with the help of a safety review committee (SRC) in advanced NSCLC subjects harboring EGFR mutant C797S or T790M. (uci.edu)
  • In Part C dose expansion study, subjects with EGFR mutant who show disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy with activity against T790M such as Osimertinib and/or no more than one platinum-based anticancer chemotherapy, are divided into 5 different cohorts based on the EGFR mutation and the anti-tumor activity of JIN-A02 is evaluated. (uci.edu)
  • This part of the study evaluates MTD using the BOIN design in advanced or metastatic NSCLC subjects with EGFR mutant C797S or T790M. (uci.edu)
  • Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. (bmj.com)
  • A compound known to target EGFR/ErbB2/ErbB4 was identified as having excellent selectivity for T790M mutant EGFR (gatekeeper mutation). (genengnews.com)
  • The current panel-track supplement was submitted to expand the intended use and indication for use of the cobas® EGFR Mutation Test v2 for the detection of the exon 20 (T790M) substitution mutation in NSCLC patients for whom Tagrisso® (osimertinib) treatment is indicated. (pdffox.com)
  • EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity. (bcm.edu)
  • Recently, a report describing EGFR-T790M as a germ-line mutation suggested that this mutation may be associated with inherited susceptibility to lung cancer. (bcm.edu)
  • In a human bronchial epithelial cell line, overexpression of EGFR-T790M displayed a growth advantage over wild-type (WT) EGFR. (bcm.edu)
  • We also screened 237 lung cancer family probands, in addition to 45 bronchoalveolar tumors, and found that none of them contained the EGFR-T790M mutation. (bcm.edu)
  • Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer. (bcm.edu)
  • HER3, which is expressed in 83 % of NSCLC tumors [3], is not known to confer resistance to EGFR TKI therapy in EGFR -mutant disease. (memoinoncology.com)
  • HER3 was expressed in the tumors of all evaluable patients and showed no correlation with time since the last EGFR TKI dose. (memoinoncology.com)
  • The small number of tumors with co-expression of mutant K-Ras and MST2 has elevated apoptosis rates. (ox.ac.uk)
  • EP344 is negative in all other tumors, while SP125 and 43B2 positive staining was found in breast carcinoma with EGFR wild type. (femtopath.com)
  • ESMO 2020 Sotorasib Is a 'Triumph of Drug Discovery' in Cancer The drug inhibits KRAS p.G12C-mutant tumors, which are seen in about 13% of patients with non-small cell lung cancer. (medscape.com)
  • The identification of this mechanism, alongside the current development of specific AXL inhibitors, provides the rationale for further studies that may improve treatment for EGFR inhibitor-resistant patients. (nature.com)
  • The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. (rcsb.org)
  • To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. (rcsb.org)
  • Inactivation of EGFR with selective inhibitors significantly reduces ERK2 activation, c-fos mRNA expression and cell proliferation. (signalchem.com)
  • EGFR tyrosine kinase inhibitors (TKIs) are the established first-line option in patients with EGFR -mutated NSCLC, although resistance inevitably develops in the long run. (memoinoncology.com)
  • A rapid, sensitive and reproducible ultra-high performance liquid chromatography mass spectrometry method was developed and validated for simultaneous determination of seven tyrosine kinase inhibitors (dasatinib, foretinib, osimertinib, gefitinib, ibrutinib, linifanib and motesanib) in human plasma samples using quizartinib as internal standard (IS). (ampksignal.com)
  • To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant mutant kinases. (genengnews.com)
  • The results revealed lead compounds with activity against clinically important mutant kinases, including ALK, LRRK2, RET, and EGFR, as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. (genengnews.com)
  • In mouse model testing in combination with Osimertinib (and also earlier TKI Gefitinib), Ocean's antibody was shown to stop human tumor progression by inducing tumor cell death and stimulating tumor suppressor genes . (yahoo.com)
  • The Company has also initiated a Phase 1 trial (KURRENT-LUNG) of tipifarnib in combination with osimertinib in EGFR-mutant non-small cell lung cancer. (biospace.com)
  • A potential treatment approach after osimertinib failure is the combination of amivantamab, a bispecific antibody targeting EGFR and MET, with the potent third-generation EGFR TKI lazertinib. (memoinoncology.com)
  • Appetite Loss as an Adverse Effect During Treatment with EGFR-TKIs in Elderly Patients with Non-small Cell Lung Cancer. (cdc.gov)
  • found that EGFR 20ins had at least 80 different insertion patterns, and lung cancer patients with EGFR 20ins showed different clinical responses to various EGFR TKIs [ 13 ]. (biomedcentral.com)
  • Ziftomenib, a potent and selective menin inhibitor, is currently in development for patients with NPM1-mutant and KMT2A-rearranged acute myeloid leukemia. (biospace.com)
  • Tipifarnib, a potent, selective and orally bioavailable farnesyl transferase inhibitor (FTI), has received Breakthrough Therapy Designation for the treatment of patients with HRAS-mutant head and neck squamous cell carcinoma (HNSCC). (biospace.com)
  • The targeting effects of IONPs conjugated to the EGFR inhibitor, cetuximab (cetuximab-IONPs), were determined with EGFR- and EGFRvIII-expressing human GBM neurospheres and GSCs. (oncotarget.com)
  • The combination of a bispecific antibody against EGFR and MET with a tyrosine kinase inhibitor (TKI) in patients with TKI-relapsed, chemotherapy-naive, EGFR-mutated advanced NSCLC is safe and shows preliminary efficacy. (nature.com)
  • The small molecule compound, Erlotinib is a receptor tyrosine kinase inhibitor (EGFR antagonist) and belongs to molecular targeted therapy Drugs. (lookchem.com)
  • Canertinib (CI-1033) is an irreversible tyrosine-kinase inhibitor with activity against EGFR (IC50 0.8 nM), HER-2 (IC50 19 nM) and ErbB-4 (IC50 7 nM). (adooq.com)
  • Compound 56 is a cell-permeable, reversible, and ATP-competitive inhibitor of tyrosine kinase activity of EGFR. (adooq.com)
  • The test is intended to be used as an aid in selecting patients with NSCLC for whom Tarceva® (erlotinib), an EGFR tyrosine kinase inhibitor (TKI), is indicated. (pdffox.com)
  • Abivertinib is a pyrrolopyrimidine-based, mutant EGFR and BTK dual inhibitor with potential across multiple indications. (itbusinessnet.com)
  • We also synthesize a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes which, upon activation, confer resistance to a BRAF inhibitor. (cdc.gov)
  • In a small correlative pilot human study, patients with EGFR-mutant metastatic NSCLC underwent FMISO-PET scans before and 10 to 12 days after erlotinib initiation. (precisionimaging.center)
  • The prognostic role of BRAF mutation in metastatic colorectal cancer receiving anti-EGFR monoclonal antibodies: a meta-analysis. (cdc.gov)
  • The involvement of Kras gene 3'-UTR polymorphisms in risk of cancer and influence on patient response to anti-EGFR therapy in metastatic colorectal cancer: a meta-analysis. (cdc.gov)
  • The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis. (cdc.gov)
  • EGFR gene copy number as a predictive biomarker for resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer treatment: a meta-analysis. (cdc.gov)
  • BRAF V600E mutation as a predictive factor of anti-EGFR monoclonal antibodies therapeutic effects in metastatic colorectal cancer: a meta-analysis. (cdc.gov)
  • Effect of BRAF V600E mutation on tumor response of anti-EGFR monoclonal antibodies for first-line metastatic colorectal cancer treatment: a meta-analysis of randomized studies. (cdc.gov)
  • FCGR2A, FCGR3A polymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer. (cdc.gov)
  • Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. (cdc.gov)
  • Vectibix is the first fully human anti-EGFR antibody approved by the U.S. Food and Drug Administration ( FDA ) for the treatment of metastatic colorectal cancer (mCRC). (amgen.com)
  • In a preclinical investigation, nude mice with human EGFR-mutant lung adenocarcinoma xenografts underwent FMISO-PET scans before and 5 days after erlotinib or empty vehicle initiation. (precisionimaging.center)
  • PCR-based assays versus direct sequencing for evaluating the effect of KRAS status on anti-EGFR treatment response in colorectal cancer patients: a systematic review and meta-analysis. (cdc.gov)
  • AXL RNA levels were assessed in a cohort of patients with available samples at baseline and at progression to anti-EGFR treatment and in the GSE5851 dataset. (bvsalud.org)
  • Furthermore, in human breast cancer, interference with the de-regulated Wnt signaling pathway reduces proliferation and survival of cancer. (wikipedia.org)
  • Further investigation revealed that mutant EGFR could activate the oncogenic STAT3 pathway via upregulated IL-6 autocrine signaling. (wikipedia.org)
  • Both mouse and human in vivo models of HER2-overexpressing breast cancers relied critically on this HER2-IL-6-STAT3 signaling pathway. (wikipedia.org)
  • Activation of EGFR triggers activation of the ERK-signaling pathway in normal gastric epithelial and colon cancer cell lines. (signalchem.com)
  • This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1). (biomedcentral.com)
  • Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras. (ox.ac.uk)
  • Here, we show that mutant K-Ras directly binds to the tumor suppressor RASSF1A to activate the apoptotic MST2-LATS1 pathway. (ox.ac.uk)
  • Akbari MR, Malekzadeh R, Nasrollahzadeh D, activates EGFR pathway signaling in the lung. (who.int)
  • Researchers from the Wellcome Sanger Institute, Addenbrooke's Hospital and their collaborators engineered a new mouse model to show for the first time how a mutation in the well-known cancer gene, EGFR initiates glioblastoma, and works with a selection from more than 200 other genes to drive the cancer. (medicalxpress.com)
  • Dr. Imran Noorani, a corresponding author previously from the Wellcome Sanger Institute, and now based at Addenbrooke's Hospital and the University of Cambridge, said: "We have created a new mouse model for studying the lethal human brain cancer, glioblastoma. (medicalxpress.com)
  • For the first time, we showed that the familiar cancer gene , EGFR is capable of initiating glioblastoma and we identified new driver genes, whose potential for therapeutic targeting deserves further exploration. (medicalxpress.com)
  • Unless otherwise indicated, our catalog and customized products are for research use only and not intended for human or animal diagnostic or therapeutic use. (ushelf.com)
  • 2020) PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas. (medicalxpress.com)
  • Human clinical trials that investigate possible MDSC modulators are highlighted, and therapeutic strategies to leverage MDSC biology in bladder cancer immunotherapy are outlined. (iospress.com)
  • Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. (rcsb.org)
  • EGFR is the receptor for members of the EGF family and is a transmembrane glycoprotein that has tyrosine kinase activity. (signalchem.com)
  • Binding of epidermal growth factor to EGFR induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation, differentiation, motility, and cell survival (1). (signalchem.com)
  • It can inhibit the phosphorylation reaction through competing with adenosine triphosphate to bind to the catalytic region of the receptor tyrosine kinase, thereby blocking the down-proliferation signaling and inhibiting the activity of the tumor cell ligand-dependent HER-1/EGFR, thus achieving the inhibition of the proliferation of tumor cells. (lookchem.com)
  • However, mutant Ras also stimulates autocrine activation of the EGF receptor (EGFR) which counteracts mutant K-Ras-induced apoptosis. (ox.ac.uk)
  • EGF receptor is concomitant to domains rearrangement in a way that domain I and III are accessible for EGF and when domain II dimerizes with another EGFR unfolded tethered form that rotated 90° on its vertical axis. (biomedcentral.com)
  • Despite significant recent advances in treating lung cancer, there is a large unmet medical need for a targeted therapy for these EGFR mutation-positive NSCLC patients, for whom chemotherapy is still the most common treatment option. (drug-dev.com)
  • The population of EGFR mutation-positive NSCLC is genetically heterogeneous - which has presented challenges in the development of effective therapies. (drug-dev.com)
  • Activation of EGFR triggers mitogenic signaling in gastrointestinal mucosa, and its expression is upregulated in colon cancers and most neoplasms (2). (signalchem.com)
  • 3 The development of molecular targeted therapies aimed at these molecular alterations has generated great optimism for the treatment of cancers such as NSCLC, and drugs targeting the EGFR tyrosine kinase domain are now available. (bmj.com)
  • Bae KM, Wang H, Jiang G, Chen MG, Lu L, Xiao L. Protein kinase C epsilon is overexpressed in primary human non-small cell lung cancers and functionally required for proliferation of non-small cell lung cancer cells in a p21/Cip1-dependent manner. (famri.org)
  • Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image. (cdc.gov)
  • Three-dimensional cultures obtained from a patient following anti-EGFR therapy resulted AXL-positive, showing resistance to anti-EGFR drugs and sensitivity to AXL inhibition. (bvsalud.org)
  • Treatment with cetuximab-IONPs resulted in a significant antitumor effect that was greater than with cetuximab alone due to more efficient, CD133-independent cellular targeting and uptake, EGFR signaling alterations, EGFR internalization, and apoptosis induction in EGFR-expressing GSCs and neurospheres. (oncotarget.com)
  • Co-occurring Alterations in Multiple Tumor Suppressor Genes are Associated with Worse Outcomes in Patients with EGFR-mutant Lung Cancer. (cdc.gov)
  • A wide variety of genomic alterations has been identified in the context of EGFR TKI resistance [1, 2]. (memoinoncology.com)
  • Furthermore, molecular alterations of the EGFR activate pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR [ 5 ]. (biomedcentral.com)
  • Kinases have been the target of extensive research to identify drugs to treat a variety of diseases in which the wild-type kinase or a mutant kinase plays a crucial role. (genengnews.com)
  • This study contains more mutant kinases than earlier large screens and helps to grow the database of compound-kinase interactions further. (genengnews.com)
  • The 76 mutant kinases are grouped according to cognate wild-type kinase. (genengnews.com)
  • In this compassionate use study, treatment of adult patients with H3K27M-mutant diffuse midline glioma with a long peptide vaccine targeting H3K27M led to vaccine-induced peripheral T cell immune responses and encouraging clinical efficacy in the majority of patients, including a durable complete response. (nature.com)
  • Thus, in CRC, mutant K-Ras transformation is supported by the wild-type allele. (ox.ac.uk)
  • Two external run controls are provided and the EGFR exon 28 wild-type allele serves as an internal, full process control. (pdffox.com)
  • Kura intends to perform initial clinical evaluation with tipifarnib while in parallel advancing KO-2806, the Company's next-generation FTI, through a Phase 1 first-in-human study. (biospace.com)
  • The Phase 1 first-in-human, open-label clinical trial of BDTX-1535 ( NCT05256290 ) consists of a dose escalation portion that evaluated the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of BDTX-1535 followed by dose expansion cohorts. (drug-dev.com)
  • The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry. (biomedcentral.com)
  • The severity of the phenotypes correlates with the expression levels of the hEGFR KI allele, which is not efficiently expressed in epithelial and bone cells, but is expressed at similar and even higher levels as the endogenous Egfr in brain and heart. (silverchair.com)
  • A significant increase in survival was found after cetuximab-IONP convection-enhanced delivery treatment of 3 intracranial rodent GBM models employing human EGFR-expressing GBM xenografts. (oncotarget.com)
  • Treatment outcomes of EGFR-TKI with or without locoregional brain therapy in advanced EGFR-mutant non-small cell lung cancer patients with brain metastases. (cdc.gov)
  • Therefore, the antibody-drug conjugate patritumab derux-tecan (HER3-Dxd) that targets HER3 is a potentially active subsequent option after failure of EGFR TKI treatment. (memoinoncology.com)
  • Determining EGFR mutation status is valuable for lung cancer patients in selecting treatment regimens. (femtopath.com)
  • We are very encouraged by the significant positive results of Abivertinib for the treatment of R/R MZL, which would be a second indication of Abivertinib for cancer treatment in addition to the potential treatment of resistant EGFR mutant positive non-small cell lung cancer," said Dr. Henry Ji, Ph.D., Chairman and CEO of Sorrento. (itbusinessnet.com)
  • Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. (amgen.com)
  • The effectiveness of Vectibix as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. (amgen.com)
  • In December 2007 , the European Medicine Agency (EMA) granted a conditional marketing authorization for Vectibix as a monotherapy for the treatment of patients with EGFR-expressing mCRC with non-mutated (wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. (amgen.com)
  • This study is a Phase I/II open-label, multi-center study to evaluate the safety, tolerability, PK, and an anti-tumor activity of JIN-A02, a 4th generation EGFR-TKI agent for oral administration, in EGFR mutant-positive, advanced NSCLC subjects who showed disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy and/or no more than a single platinum-based anticancer chemotherapy. (uci.edu)
  • Indeed, upon binding to ligands like EGF or TGF-α, the EGFR undergoes autophospholrylation that leads to the activation of several signal-transduction cascades, and cell cycle-progression [ 4 ]. (biomedcentral.com)
  • 2. Kobayashi S, et al: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. (signalchem.com)
  • Cetuximab biosimilar L234A L235A P329G (LALAPG) Fc silent mutant (anti-human EGFR monoclonal antibody) is used for ELISA, neutralization, in vivo functional assays such as bioanalytical PK and ADA assays, and those in vitro and in vivo assays for studying biological pathways affected by cetuximab. (ushelf.com)
  • Fluorescence microscopy and Prussian blue staining showed increased uptake of cetuximab-IONPs by EGFR- as well as EGFRvIII-expressing GSCs and neurospheres in comparison to cetuximab or free IONPs. (oncotarget.com)
  • Recombinant human EGFR (A767_S768insTLA) (695-end) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. (signalchem.com)
  • The developed method was successfully applied to in-vitro human microsomal metabolic stability study. (ampksignal.com)
  • IHC analysis of EP344, SP125 and 43B2 on human tissue microarray (TMA) comprising 16 types of normal tissues showed that all 3 antibodies stained negatively in all normal cells. (femtopath.com)
  • The phase I U31402-A-U102 dose escalation and dose expansion study tested HER3-Dxd in patients with EGFR-TKI-resistant NSCLC. (memoinoncology.com)
  • No dose adjustment is needed in patients with mild renal impairment (eGFR between 60 and 90 mL/minute). (who.int)
  • We sought to determine whether FMISO positron emission tomography (FMISO-PET) could detect changes in hypoxia in vivo in response to EGFR-targeted therapy. (precisionimaging.center)