|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Isogenic NSCLC cell clones expressing wild-type (WT) and mutated (G12C) KRAS were used to determine the response to BEZ235 and BKM120.
|
27283493 |
2016 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib.
|
22617245 |
2012 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The present studies demonstrate that silencing MUC1-C in A549/KRAS(G12S) and H460/KRAS(Q61H) NSCLC cells is associated with downregulation of AKT signaling and inhibition of growth.
|
25245423 |
2014 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We develop a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets.
|
31668570 |
2019 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
NSCLC cell lines with mutant KRas-Gly12Asp had activated phosphatidylinositol 3-kinase (PI-3-K) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling, whereas those with mutant KRas-Gly12Cys or mutant KRas-Gly12Val had activated Ral signaling and decreased growth factor-dependent Akt activation.
|
22247021 |
2012 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
KRAS G12C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer.
|
28407465 |
2017 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
KRAS G12C, the most common RAS mutation found in non-small-cell lung cancer, has been the subject of multiple recent covalent small-molecule inhibitor campaigns including efforts directed at the guanine nucleotide pocket and separate work focused on an inducible pocket adjacent to the switch motifs.
|
28781083 |
2017 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition.
|
30327306 |
2019 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.
|
23313110 |
2013 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSCLC patient.
|
24200637 |
2014 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Recently, G12C KRAS mutation in isogenic NSCLC cell line has been shown to be a key player in promoting metabolic rewiring mainly through the regulation of glutamine metabolism to fuel growth and proliferation.
|
27329432 |
2016 |
|
rs121913530
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
In NSCLC GLY12Cys mutations, resulting from a codon 12 GGT>TGT substitution, were observed in 44% compared to 10% for CRC.
|
24331409 |
2014 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
In particular, a number of EGFR mutants that demonstrate ligand-independent signaling are common in non-small cell lung cancer (NSCLC), including kinase domain mutations L858R (also called L834R) and exon 19 deletions (e.g., ΔL747-P753insS), which collectively make up nearly 90% of mutations in NSCLC.
|
26337388 |
2015 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
EGFR)-targeted drugs have been the first-line treatment for patients with <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC), especially exon 19 deletions and L858R mutation in exon 21.
|
31686847 |
2019 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
EGFR tyrosine kinase inhibitors versus chemotherapy as first-line therapy for non-small cell lung cancer patients with the L858R point mutation.
|
27811976 |
2016 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring EGFR Exon 19 Deletion and Exon 21 L858R Substitution.
|
28110331 |
2017 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Non-small cell lung cancer (NSCLC) patients with L858R or exon 19 deletion mutations in epidermal growth factor receptor (EGFR) have good responses to the tyrosine kinase inhibitor (TKI), gefitinib.
|
21858220 |
2011 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Seven of these mutations were novel, and one was the L858R mutation described in non-small-cell lung cancer.
|
18998063 |
2009 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation).
|
28489575 |
2017 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Compound 12k exhibited strong and selective EGFR L858R/T790M inhibitory activity (IC50 = 0.047 μM) and displayed antiproliferative effects on EGFR mutation NSCLC cell lines HCC827 (del E746_A750) and H1975 (L858R/T790M) with IC50 values of 0.007 and 0.029 μM, respectively.
|
23668441 |
2013 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Subgroup analysis in different age groups (10 yr as an interval) and N stages (stratified by N0, N1, N2, and N3) also indicated above-mentioned trends.NSCLC patients with 19 Del are more likely to be young and have lymphatic metastasis than those with L858R.
|
26554801 |
2015 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Although almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy.
|
29748209 |
2018 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
It is approved for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, and for patients with T790M-positive advanced NSCLC whose disease has progressed on or after EGFR-TKI therapy.
|
30875094 |
2019 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in nonsmall cell lung cancer.
|
30030903 |
2018 |
|
rs121434568
|
|
Non-Small Cell Lung Carcinoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Exon 19 deletions and exon 21 L858R substitutions are the most common mutations, accounting for approximately 90% mutations in NSCLC; these are termed classic mutations and result in high sensitivity to tyrosine kinase inhibitors (TKIs).
|
31367543 |
2019 |