Approximately 20-25% of NSCLC harbor treatable driver mutations/rearrangements; epidermal growth factor receptor mutation, anaplastic lymphoma kinase and ROS-1 gene rearrangements are the main alterations for which a Food and Drug Administration-approved tyrosine kinase inhibitor can be used.Because of recent technological advances, high sensitivity assays with a broad range of genomic targets have become more easily accessible in clinical practice, which has led to an increased detection of coexisting driver alterations in patients with advanced NSCLC.
We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients.
We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion.
We describe a case of an 18 years old woman, never smoker, with NSCLC <i>ROS1+</i> and miliary brain metastases treated with crizotinib and radiotherapy.
We also examined a separate database of ROS1-rearranged NSCLCs identified through the commercial FoundationOne assay (Foundation Medicine, Cambridge, MA).
Here we present the evidence concerning entrectinib, an ALK/ROS1/NTRK inhibitor developed across different tumor types harboring rearrangements in these genes, in the context of ROS1-driven NSCLC.
These findings demonstrate that zerumbone induces mitochondrial apoptosis and enhances the susceptibility to cisplatin in NSCLC cells, which are, at least partially, mediated through activation of p53 signaling and promotion of ROS generation.
Reflex simultaneous genotypic screening for EGFR by peptide nucleic acid clamping, and ALK and ROS1 by fluorescence in situ hybridization (FISH) was performed on consecutive NSCLC cases at the time of initial pathologic diagnosis.
The c-ros oncogene 1 (ROS1) fusion is almost mutually exclusive to epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in non-small cell lung cancer (NSCLC), and it is not seen in the literature for patients to exhibit three mutations.
Lorlatinib is an oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1) kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer (NSCLC).
Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes.
Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities.
Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC.
The investigational ALK inhibitor lorlatinib, whose early clinical activity was first reported last year, continues to look promising in advanced ALK-positive or ROS1-positive non-small cell lung cancer.
Cigarette smoke extract induces EGFR-TKI resistance via promoting EGFR signaling and ROS generation in NSCLC cell lines which could be suppressed by NAC.
EGFR activating mutations, EML4/ALK translocation, ROS1 rearrangements) in a selected population of patients affected by non small cell lung cancer (NSCLC) translated into effective treatments for this small but well defined fraction of patients, driven by the use of predictive biomarkers of efficacy for targeted agents.
Crizotinib was approved by the US Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)- or ROS1-positive non-small cell lung cancer (NSCLC).
Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 392 patients with NSCLC were screened for ROS1 fusions by multiplex RT-PCR and all ROS1 fusions were validated by direct sequencing.
Both <i>in vivo</i> and <i>in vitro</i> studies verified that butein exerted anti-NSCLC effect through activating endoplasmic reticulum (ER) stress-dependent reactive oxygen species (ROS) generation.
We identified 453 patients who had NSCLC with an oncogenic alteration in ALK receptor tyrosine kinase gene (ALK), ROS1, or MET proto-oncogene, receptor tyrosine kinase gene (MET) and were treated with crizotinib (11 with and 442 without prior ICI therapy).
We conducted a multi-institutional prospective study including consecutive EGFR, ALK, or ROS1-altered NSCLC patients with TKI resistance from 12 Spanish institutions.