Pub. Date : 2020 May
PMID : 32208297
11 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | A novel ROS1 G2032 K missense mutation mediates lorlatinib resistance in a patient with ROS1-rearranged lung adenocarcinoma but responds to nab-paclitaxel plus pembrolizumab. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 2 | INTRODUCTION: ROS1-rearranged non-small cell lung cancer (NSCLC) has demonstrated promising response to lorlatinib; however, no targeted therapy is available after failure of lorlatinib and information on acquired resistance mechanisms mediating lorlatinib resistance among ROS1-rearranged NSCLC patients is limited. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 3 | INTRODUCTION: ROS1-rearranged non-small cell lung cancer (NSCLC) has demonstrated promising response to lorlatinib; however, no targeted therapy is available after failure of lorlatinib and information on acquired resistance mechanisms mediating lorlatinib resistance among ROS1-rearranged NSCLC patients is limited. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 4 | INTRODUCTION: ROS1-rearranged non-small cell lung cancer (NSCLC) has demonstrated promising response to lorlatinib; however, no targeted therapy is available after failure of lorlatinib and information on acquired resistance mechanisms mediating lorlatinib resistance among ROS1-rearranged NSCLC patients is limited. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 5 | We report a ROS1-rearranged NSCLC patient who responded to immunochemotherapy after acquisition of ROS1 G2032K-mediated lorlatinib resistance. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 6 | We report a ROS1-rearranged NSCLC patient who responded to immunochemotherapy after acquisition of ROS1 G2032K-mediated lorlatinib resistance. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 7 | RESULTS: NGS analysis revealed the detection of an acquired ROS1 G2032 K after failure from lorlatinib. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 8 | Homology modeling revealed the conformational change in the inhibitor binding site induced by the ROS1 G2032 K that disrupted lorlatinib binding. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 9 | In vitro experiments using patient-derived cells bearing concurrent CD74-ROS1-rearrangement and ROS1 G2032 K demonstrated half-maximal inhibitory concentration IC50 of 730.2 nM for lorlatinib, 812.1 nM for entrectinib, and 1546 nM for crizotinib, indicating resistance to these inhibitors. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 10 | In vitro experiments using patient-derived cells bearing concurrent CD74-ROS1-rearrangement and ROS1 G2032 K demonstrated half-maximal inhibitory concentration IC50 of 730.2 nM for lorlatinib, 812.1 nM for entrectinib, and 1546 nM for crizotinib, indicating resistance to these inhibitors. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |
| 11 | CONCLUSION: ROS1 G2032 K is a novel mutation that mediates resistance to lorlatinib. | lorlatinib | ROS proto-oncogene 1, receptor tyrosine kinase | Homo sapiens |