The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR-mutant and wild-type lung tumors.
The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases.
But, additionally, we found that depending on its subcellular localization, IKKα has non-overlapping roles in the activation of other different pathways known for their key implication in lung cancer progression: while cytoplasmic IKKα increases EGFR and NF-κB activities in lung tumor cells, nuclear IKKα causes lung tumor progression through c-Myc, Smad2/3 and Snail activation.
The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors.
We previously demonstrated that wild type and mutant EGFRs repress the expression of the ARF tumor suppressor to promote the survival of lung tumor cells.
Epidermal growth factor receptor (EGFR) activation was reported to upregulate programmed death-ligand 1 (PD-L1) expression in lung cancer cells and subsequently contribute to immune escape, indicating its critical role in EGFR-driven lung tumors.
Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.
(Theranostics 2018; 8(7):1808-1823. doi:10.7150/thno.23177) it was shown that lung tumors resistant to the EGFR-inhibitor (Erlotinib), reprogram their metabolism and acquire a pro-survival dependency on Phosphoglycerate Dehydrogenase (PHGDH) that can be targeted to eliminate resistant tumors.
These results suggest that targeting EGFR ligands may benefit patients who carry EGFR-mutant lung tumors but will not benefit patients with KRAS-mutant lung tumors.
According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) derived for thoracic RT for lung tumor after EGFR TKI use and tumor response (group 2) compared with EGFR TKI treatment alone (group 1) was 0.72 (0.60-0.85).
We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRAS<sup>G12D</sup>-driven lung tumors.
In contrast, specific epidermal growth factor receptor (EGFR) inhibitors have been used successfully against lung tumors displaying activating mutations in the kinase domain of EGFR.