Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1.
The present study sought to investigate the effects of quinalizarin on proliferation, apoptosis and reactive oxygen species (ROS) generation in lung cancer.
Multiple oncogene fusions beyond ALK receptor tyrosine kinase (ALK), RET, and ROS1 fusion has been described in lung cancer, especially in lung adenocarcinomas without common oncogenic mutations.
We have used human lung cancer cell lines carrying a plasmid vector containing a (CA)(13) microsatellite sequence to study frameshift mutations mediated by ROS-generating chemicals paraquat and hydrogen peroxide.
We aimed to compare two recent amplicon-based RNA-sequencing techniques: FusionPlex<sup>®</sup> Alk Ret Ros1 v2 Kit (Archer<sup>®</sup> ) with FHS-003Z-12-Human Lung Cancer Panel (Qiagen<sup>®</sup> ) and assessed the accuracy of the data for therapy management.
Sadly, crizotinib resistance in ROS1 is a frequent occurrence which poses a major clinical challenge in the successful treatment of ROS1lung cancer; hence, the discovery of the second and third generation ROS1 inhibitors is of utmost importance.
The identification of the location of the rs9387478 single nucleotide polymorphism in the genomic interval containing the DCBLD1 and ROS1 genes, together with the finding that the rs9387478 polymorphism correlates with EGFR mutation status, may have important implications for therapeutic approaches targeting EGFR or ROS1 in patients with lung cancer.
Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations.
Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK-positive cases and use of IHC to screen for potentially positive cases, can be used to enrich for the likelihood of identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time-consuming FISH testing in all cases.
Collectively, these data suggest that each of these two ROS1-fusion genes acts as a driver for the pathogenesis of lung adenocarcinoma in vivo The TG mice developed in this study are expected to serve as valuable tools for exploring novel therapeutic agents against ROS1-fusion-positive lung cancer.
Multiplex fluorescence in situ hybridisation to detect anaplastic lymphoma kinase and ROS proto-oncogene 1 receptor tyrosine kinase rearrangements in lung cancer cytological samples.
Although full-length ROS1 is expressed in some ROS1-non-rearranged cases, we showed that establishment of an optimal set of interpretative criteria makes ROS1 immunohistochemistry a valuable method to rapidly and accurately screen lung cancer patients for appropriate molecular therapy.
Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement.
We analyzed cases with lung adenocarcinomas for representative genomic aberrations, evaluated the response to the multitargeted MET/ALK/ROS1 crizotinib TKI in cases with MET aberrations and profiled lung cancer cell lines with the aforementioned genomic changes.