Wnt/β‑catenin signaling and sex‑determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to epidermal growth factor receptor‑targeting therapy in lung cancer.
With the goal of treating mutated EGFR-mediated lung cancer, we demonstrate the use of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system to discriminate between the oncogenic mutant and wild-type EGFR alleles and eliminate the carcinogenic mutant EGFR allele with high accuracy.
With multiple clinical trials under way targeting mutant EGFR in patients with lung cancer, Maity and colleagues address important aspects of a MIG6-EGFR signaling axis using genetically engineered mouse models expressing mutated EGFRs on the MIG6-deficient background.
With its recent approval by the US Food and Drug Administration, gefitinib adds to the list of recommended first-line treatments for lung cancer harboring EGFR mutations, which hitherto includes erlotinib and afatinib.
Why are mutation rates in epidermal growth factor receptor (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2) higher in lung cancer from never smokers than that from smokers?Question 62.
While they produce dramatic responses in a subset of patients-primarily those with activating EGFR mutations-remissions are typically limited to several months due to acquired drug resistance, frequently associated with the secondary T790M mutation in EGFR.In this issue of Cancer Cell, Li et al. report that an irreversible EGFR kinase inhibitor, HKI-272, had limited activity in a mouse lung cancer model driven by an EGFR mutant harboring T790M and an activating mutation.
While the advent of third-generation therapies has dramatically changed the treatment paradigm for EGFR-mutated lung cancer, resistance to these agents inevitably emerges.
While the EGFR mutation rate was lower in the younger group (52.5% versus 60.6%, P = 0.001), the primary site of lung cancer and stage distribution were not significantly different.
When the chimeric ubiquitin ligases were introduced into lung cancer SPC-A1 cells, they effectively associated with EGFR, promoted its ubiquitination and degradation, and as a result, blocked the downstream PI3K-Akt signal pathway.
When cocultured with EGFR mutation positive lung cancer cells, these CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the absence of gefitinib, they did not affect cancer cell viability.
Well-characterized kinase molecular target in lung cancer, in particular in non-small cell lung cancer (NSCLC), is the activated epidermal growth factor receptor (EGFR) pathway.
We were able to detect these mutations in 37 (97%) of 38 FFPE lung cancer tissue samples within 60 minutes with the SmartAmp2 assay and to confirm the correlation between EGFR mutations in FFPE tissues and gefitinib responsiveness.
We used this approach to model different mechanisms of lung cancer cell resistance to EGFR inhibitors and to assess effects of combined drug therapies.
We used multiple lung cancer cell lines to develop and characterize EGFR:GRB2 PLA and correlated this assay with established biochemical measures of EGFR signaling.
We used a nanofluidic digital PCR array platform and 16 cell lines and 20 samples of genomic DNA from resected tumors (stages I-III) to quantify the relative numbers of copies of the EGFR gene and to detect mutated EGFR alleles in lung cancer.
We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib + THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting.
We therefore investigated lung cancer cell lines for alterations in EGFR gene copy number, enhanced expression of EGFR and other HER family members, and EGFR coding sequence mutations and correlated these findings with response to treatment with the EGFR inhibitors and the kinetics of ligand-induced signaling.
We summarize updates on EGFR targeted therapies that were presented during the sixth annual Targeted Therapies for the Treatment of Lung Cancer Conference in Los Angeles, CA; January 27-28, 2006.
We sought to measure epidemiology of lung cancer among AI receiving diagnosis or treatment in Minnesota cancer referral centers as well as rate of EGFR testing.
We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors.
We show that EGFR activity is inhibited by erlotinib in H1650, a lung cancer cell line that bears a sensitizing EGFR mutation, but that H1650 is not killed.