Prediction of Resistant Mutations against Upcoming ALK-TKIs, Repotrectinib (TPX-0005) and Ensartinib (X-396)
Doi, Y.; Tagaya, H.; Noge, A.; Semba, K.
Show abstract
ALK gene rearrangement is observed in approximately 4% of patients with non-small cell lung cancer. These individuals benefit clinically from a range of approved ALK-TKIs; however, using many ALK-TKIs in a row will always result in resistant compound mutations in the kinase domain. Therefore, next-generation ALK-TKIs which are potent to these resistant mutations are still under development. In this context, preclinical prediction of resistant mutations generated by developing ALK-TKIs will provide useful information about the effective sequential treatment of ALK-TKIs. In this study, we developed a simple error-prone PCR-based mutation prediction system, and as a model study, we predicted resistant mutations against upcoming ALK-TKI, repotrectinib, and ensartinib. According to the predictive mutation patterns, repotrectinib and ensartinib may be used as second-line therapeutic options following the first-line alectinib treatment.
Matching journals
The top 16 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Selective Impact of ALK and MELK Inhibition on ERα Stability and Cell Proliferation in Cell Lines Representing Distinct Molecular Phenotypes of Breast Cancer 93%
- Rapid Resistance To Bet Inhibitors Is Mediated By Fgfr1 In Glioblastoma 93%
- Collateral Responses to Classical Cytotoxic Chemotherapies are Heterogeneous and Sensitivities are Sparse 93%
Similar papers in this journal
Similar papers in this journal
- NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model 94%
- A chemical screen based on an interruption of zebrafish gastrulation identifies the HTR2C inhibitor Pizotifen as a suppressor of EMT-mediated metastasis 93%
- Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma 93%
Similar papers in this journal
- Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD 93%
- Selective Regulation of Tuft Cell-Like Small Cell Lung Cancer by Novel Transcriptional Co-activators C11orf53 and COLCA2 92%
- Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages 91%
Similar papers in this journal
- TKI Type Switching Overcomes ROS1 L2086F in ROS1 Fusion-Positive Cancers 95%
- Anti-EGFR aptamer exhibits direct anti-cancer effects in NSCLC cells harboring EGFR L858R mutations 92%
- Overcoming Resistance to BRAFV600E Inhibition in Melanoma by Deciphering and Targeting Personalized Protein Network Alterations 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.