Our study revealed that concurrent genomic alterations can further stratify KRAS-mutant lung adenocarcinoma patients into various subgroups with distinctive therapeutic responses and differential survival outcomes.
The KRAS gene is the second most frequently mutated gene in LUAC and the majority of KRAS mutations are one of three classical activating mutations (G12, G13, and Q61).
While PD-L1+/-IDO1 expression is observed in association with HLA class I expression, cytotoxic T lymphocyte/Th1 microenvironments, EGFR wild-type, and KRAS mutations, isolated IDO1 expression does not demonstrate these associations, suggesting that IDO1 may serve a distinct immunosuppressive role in lung adenocarcinomas.
To identify which proteins are involved in the restoration of this sensitivity and to provide new therapeutic targets for mutant-KRASlung adenocarcinoma, we performed an iTRAQ quantitative proteomic analysis after subcellular fractionation of H358-NSCLC treated with gefitinib and KDACi (TSA/NAM) versus gefitinib alone.
This study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.
Whereas BM incidence showed a tendency to increase as the M staging increased in patients with EGFR-mutant lung ADC (p < 0.001, trend test), there was no linear trend between M staging and ALK (p = 0.469, trend test) or K-RAS mutations (p = 0.066, trend test).
Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics.
Patients with surgically resected lung adenocarcinoma (n = 72) were enrolled, including 12 patients with KRAS mutations and 60 patients with EGFR mutations.
Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites.
The KRAS-positive group included higher proportions of cases with an inflammatory background (100%), predominantly papillary architecture (75%), and papillary-type ADC pattern (75%) compared with the EGFR-positive group and the other group, which included ALK and ROS1 gene rearrangements.
<i>KRASp.G12C</i>, which occurs in approximately 14% of lung adenocarcinomas, 3-5% of colorectal cancers, and low levels in other solid tumors, represents an attractive therapeutic target for covalent inhibitors.
Nanoparticle uptake, cellular distribution of nucleic acids, cytotoxicity and gene knock down to interfere with cancer hallmarks, uncontrolled proliferation and migration, were evaluated in KRASG12S mutant A459 cells, a lung adenocarcinoma cell line.
Elesclomol might provide an alternative treatment approach for patients with KRAS mutant lung adenocarcinoma and other solid tumor malignancies that harbor KRAS mutations.
REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutant lung adenocarcinoma with low expression of TTF-1 (KC subtype).
Some other studies performed indicate also the potential role of DMF in cancers, which are dependent on the NRF2 antioxidant and cellular detoxification program, such as KRAS-mutated lung adenocarcinoma.