{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Berko ER"],"funding":["NCATS NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","Doris Duke Charitable Foundation","U.S. Department of Health & Human Services | NIH | National Cancer Institute","Cookies for Kids Cancer The EVAN Foundation","NCI NIH HHS","Solving Kids' Cancer","NIGMS NIH HHS"],"pagination":["2601"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10163008"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Activating point mutations in Anaplastic Lymphoma Kinase (ALK) have positioned ALK as the only mutated oncogene tractable for targeted therapy in neuroblastoma. Cells with these mutations respond to lorlatinib in pre-clinical studies, providing the rationale for a first-in-child Phase 1 trial (NCT03107988) in patients with ALK-driven neuroblastoma. To track evolutionary dynamics and heterogeneity of tumors, and to detect early emergence of lorlatinib resistance, we collected serial circulating tumor DNA samples from patients enrolled on this trial. Here we report the discovery of off-target resistance mutations in 11 patients (27%), predominantly in the RAS-MAPK pathway. We also identify newly acquired secondary compound ALK mutations in 6 (15%) patients, all acquired at disease progressio"],"journal":["Nature communications"],"pubmed_title":["Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma."],"pmcid":["PMC10163008"],"funding_grant_id":["CA217959","R35 GM122485","2019120","CA140198","TL1 TR001880","P01 CA217959","R01 CA140198","T32 CA009615","R35 CA220500","U01 CA250044","U01 CA227550","GM122485"],"pubmed_authors":["Maris JM","Lemmon MA","Marachelian A","Kennedy A","Ghazarian S","Goldsmith KC","Casey C","Wu MA","Kalna J","Daniels A","Park JR","Smith CM","Krytska K","Matkar S","Berko ER","Witek GM","Petrova ZO","Mosse YP","Pavlick D","Gostuski I","Gerelus M","Radhakrishnan R"],"additional_accession":[]},"is_claimable":false,"name":"Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma.","description":"Activating point mutations in Anaplastic Lymphoma Kinase (ALK) have positioned ALK as the only mutated oncogene tractable for targeted therapy in neuroblastoma. Cells with these mutations respond to lorlatinib in pre-clinical studies, providing the rationale for a first-in-child Phase 1 trial (NCT03107988) in patients with ALK-driven neuroblastoma. To track evolutionary dynamics and heterogeneity of tumors, and to detect early emergence of lorlatinib resistance, we collected serial circulating tumor DNA samples from patients enrolled on this trial. Here we report the discovery of off-target resistance mutations in 11 patients (27%), predominantly in the RAS-MAPK pathway. We also identify newly acquired secondary compound ALK mutations in 6 (15%) patients, all acquired at disease progressio","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-05-28T20:13:41.861Z","creation":"2025-04-05T11:24:12.428Z"},"accession":"S-EPMC10163008","cross_references":{"pubmed":["37147298"],"doi":["10.1038/s41467-023-38195-0"]}}