Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.

ABSTRACT:

Purpose

ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway.

Experimental design

We compared different ALK inhibitors in preclinical models prior to

SUBMITTER: Tucker ER 

PROVIDER: S-EPMC10068437 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature