In summary, we describe a patient with relapsed, refractory neuroblastoma harboring the ALK F1174L mutation resistant to the first-generation ALK inhibitor crizotinib combined with chemotherapy in whom lorlatinib induced a durable complete remission of 13 mo. However, as is often the case with targeted therapeutic approaches, resistance, potentially mediated by new genomic alterations including CDK4 and FGFR1 amplification and NRAS mutation, led to disease recurrence. Our case provides an example of clinical benefit made possible by the development of next-generation ALK inhibitors but also highlights the need for increased understanding of mechanisms of acquired resistance. We propose that molecular monitoring during therapy may guide rational combination multidrug approaches to overcome and prevent resistance. READ ARTICLE
Cold Spring Harbor: Molecular Case Studies DOI:10.1101/mcs.a006064
Authors: Tingting Liu, Matthew D., Merguerian, Steven P. Rowe, Christine A. Pratilas, Allen R. Chen and Brian H. Ladle