scholarly journals Circulating tumor DNA profiling by next generation sequencing reveals heterogeneity of crizotinib resistance mechanisms in a gastric cancer patient with MET amplification

Oncotarget ◽  
2017 ◽  
Vol 8 (16) ◽  
pp. 26281-26287 ◽  
Author(s):  
Juan Du ◽  
Xue Wu ◽  
Xiaoling Tong ◽  
Xiaonan Wang ◽  
Jia Wei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patient ◽  
Gastric Cancer Patient ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Next Generation ◽  
Met Amplification ◽  
Tumor Dna ◽  
Generation Sequencing

scholarly journals Mechanisms of Acquired Resistance to Savolitinib, a Selective MET Inhibitor in MET-Amplified Gastric Cancer

2020 ◽  
pp. 222-232 ◽  
Author(s):  
Melanie M. Frigault ◽  
Aleksandra Markovets ◽  
Barrett Nuttall ◽  
Kyoung-Mee Kim ◽  
Se Hoon Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Met Inhibitor ◽  
Tumor Dna ◽  
Generation Sequencing

PURPOSE Some gastric cancers harbor MET gene amplifications that can be targeted by selective MET inhibitors to achieve tumor responses, but resistance eventually develops. Savolitinib, a selective MET inhibitor, is beneficial for treating patients with MET-driven gastric cancer. Understanding the resistance mechanisms is important for optimizing postfailure treatment options. PATIENTS AND METHODS Here, we identified the mechanisms of acquired resistance to savolitinib in 3 patients with gastric cancer and MET-amplified tumors who showed a clinical response and then cancer progression. Longitudinal circulating tumor DNA (ctDNA) is useful for monitoring resistance during treatment and progression when rebiopsy cannot be performed. RESULTS Using a next-generation sequencing 100-gene panel, we identified the target mechanisms of resistance MET D1228V/N/H and Y1230C mutations or high copy number MET gene amplifications that emerge when resistance to savolitinib develops in patients with MET-amplified gastric cancer. CONCLUSION We demonstrated the utility of ctDNA in gastric cancer and confirmed this approach using baseline tumor tissue or rebiopsy.

Correlation of genomic alterations between tumor tissue and circulating tumor DNA by next-generation sequencing

2018 ◽  
Vol 144 (11) ◽  
pp. 2167-2175 ◽  
Author(s):  
Ya-Sian Chang ◽  
Hsin-Yuan Fang ◽  
Yao-Ching Hung ◽  
Tao-Wei Ke ◽  
Chieh-Min Chang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Genomic Alterations ◽  
Tumor Dna ◽  
Generation Sequencing
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