Identification of nicotinamide aminonaphthyridine compounds as potent RET kinase inhibitors and antitumor activities against RET rearranged lung adenocarcinoma.
In the 16 RET-positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET-KIF5B fusion partners.
We constructed a tissue microarray (TMA) comprising 581 resected tumor tissues from patients with lung adenocarcinoma and analyzed the microarray by both FISH (using RET break-apart and KIF5B-RET SY translocation probes) and a commercial RET transcript assay.
Gene rearrangements, including ALK, ROS1 and RET, and gene mutations, including epidermal growth factor receptor (EGFR), HER2, Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide‑3‑kinase, catalytic, α polypeptide and MET, have been identified in lung adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example erlotinib, gefitinib and afatinib, which are EGFR inhibitors.
Collectively, these findings demonstrate that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation.<i></i>.
As an alternative, we can also hypothesize that this was a case of fusion of two tumoral tissues deriving from a DSV-PTC and a metastasis of a KIF5B/RET positive lung adenocarcinoma.
Among 795 East Asian patients who underwent a surgical procedure for NSCLC, we screened 45 patients with quintuple-negative (EGFR-negative/KRAS-negative/anaplastic lymphoma kinase gene [ALK]-negative/ROS1-negative/ret proto-oncogene [RET]-negative) lung adenocarcinomas by using reverse-transcriptase polymerase chain reaction and found 17 patients (37.8%) with METex14 skipping.
These results indicate that KIF5B-RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma.
We performed amplification refractory mutation system (ARMS) fluorescence quantitative PCR to detect the gene status of EGFR, ALK, ROS1 and RET in resected samples from 280 patients who were confirmed to have primary lung adenocarcinomas with N1-N2 lymph node metastasis.
However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients.
Identification of a novel partner gene, KIAA1217, fused to RET: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma.
Between July 13, 2012, and April 30, 2016, 26 patients with RET-rearranged lung adenocarcinomas were enrolled and given cabozantinib; 25 patients were assessable for a response.
Nine hundred ninety-seven patients with KRAS/EGFR/ALK wildtype lung adenocarcinomas were analyzed using fluorescence in situ hybridization for RET fusions.
We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying.
Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians.
Fusions of the anaplastic lymphoma receptor tyrosine kinase gene (ALK), ret proto-oncogene (RET), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1), B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), and neuregulin 1 gene (NRG1) and intronic MMNG HOS Transforming gene (MET) mutations are druggable oncogene alterations in lung adenocarcinoma that cause expression of aberrant transcripts.