Entrectinib in neurotrophic receptor tyrosine kinase fusion-positive (NTRK- fp) non-small cell lung cancer (NSCLC): integrated analysis of patients enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001

2020 ◽  
Author(s):  
L Paz-Ares ◽  
RC Doebel ◽  
AF Farago ◽  
S Liu ◽  
SP Chawla ◽  
...  
2016 ◽  
Vol 22 (14) ◽  
pp. 3663-3671 ◽  
Author(s):  
Masato Terashima ◽  
Yosuke Togashi ◽  
Katsuaki Sato ◽  
Hiroshi Mizuuchi ◽  
Kazuko Sakai ◽  
...  

Dermatology ◽  
1999 ◽  
Vol 199 (4) ◽  
pp. 290-295 ◽  
Author(s):  
G. Krähn ◽  
K.M. Greulich ◽  
G. Bezold ◽  
C. Dieterle ◽  
H. Wolff ◽  
...  

2007 ◽  
Vol 292 (6) ◽  
pp. L1488-L1494 ◽  
Author(s):  
Ramasamy Jagadeeswaran ◽  
Sujatha Jagadeeswaran ◽  
Vytas P. Bindokas ◽  
Ravi Salgia

Small cell lung cancer (SCLC) is a difficult disease to treat and sometimes has overexpression or mutation of c-Met receptor tyrosine kinase. The effects of c-Met/hepatocyte growth factor (c-Met/HGF, ligand for c-Met) on activation of reactive oxygen species (ROS) was determined. HGF stimulation of c-Met-overexpressing H69 SCLC cells (40 ng/ml, 15 min) resulted in an increase of ROS, measured with fluorescent probe 2′-7′-dichlorofluorescein diacetate (DCFH-DA) or dihydroethidine (DHE) but not in c-Met-null H446 cells. ROS was increased in juxtamembrane (JM)-mutated variants (R988C and T1010I) of c-Met compared with wild-type c-Met-expressing cells. ROS was significantly inhibited by preincubation of SCLC cells with pyrrolidine dithiocarbamate (PDTC, 100 μM) and/or SU11274 (small molecule c-Met tyrosine kinase inhibitor, 2 μM) for 3 h. PDTC and SU11274 also abrogated the HGF proliferative signal and cell motility in a cooperative fashion. H2O2 treatment of SCLC cells (over 15 min) led to phosphorylation of c-Met receptor tyrosine kinase and further upregulated downstream phosphorylation of phospho-AKT, ERK1/2, and paxillin in a dose-dependent manner (125 μM to 500 μM). c-Met is an important target in lung cancer, and the pathways responsible for ROS generation together may provide novel therapeutic intervention.


2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii22-iii22
Author(s):  
Dennis London ◽  
Dev Patel ◽  
Bernadine Donahue ◽  
Ralph Navarro ◽  
Jason Gurewitz ◽  
...  

Abstract Purpose Patients with non-small cell lung cancer (NSCLC) metastatic to the brain increasingly are living longer due to improvements in systemic therapy and local modalities. The risk of new brain metastases when these patients stop systemic therapy is unknown. Recognizing patterns of new tumor occurrence is necessary to determine the frequency of follow-up and the need for further treatment. Methods We included patients in a prospective registry who had non-small cell lung cancer (NSCLC) brain metastases, discontinued systemic therapy for at least 90 days, and underwent active surveillance. 63 patients with 73 off-periods were studied. The risk factors for the development of new tumors were determined using Cox regression and multi-state Markov modeling. Results The median time to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase pathways (e.g. KRAS, EGFR) were more likely to develop new tumors (HR: 2.21, 95% CI: 1.25–3.91, p=6.3 x 10–3; HR: 2.03, 95% CI: 1.09–3.77, p=0.026, respectively). Conclusion The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or receptor tyrosine kinase pathway mutations have a higher rate of new metastases and should be followed more closely.


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