Exceptional response to the ALK and ROS1 inhibitor lorlatinib and subsequent mechanism of resistance in relapsed ALK F1174L-mutated neuroblastoma.

ABSTRACT: Treatment of high-risk neuroblastoma typically incorporates multiagent chemotherapy, surgery, radiation therapy, autologous stem cell transplantation, immunotherapy, and differentiation therapy. The discovery of activating mutations in ALK receptor tyrosine kinase (ALK) in ∼8% of neuroblastomas opens the possibility of further improving outcomes for this subset of patients with the addition of ALK inhibitors. ALK inhibitors have shown efficacy in tumors such as non-small-cell lung cancer and anaplastic large cell lymphoma in which wild-type ALK overexpression is driven by translocation events. In contrast, ALK mutations driving neuroblastomas are missense mutations in the tyrosine kinase domain yielding constitutive activation and differing sensitivity to available ALK inhibitors. W

SUBMITTER: Liu T 

PROVIDER: S-EPMC8327881 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature