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Open Access 11-03-2025 | Neuroblastoma | REVIEW

15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL

Authors: Salma Elmenawi, Mohamed Fawzy

Abstract

Purpose of review

This review provides a comprehensive understanding of the ALK gene, encompassing its prevalence, genetic alterations, and significance in neuroblastoma diagnosis, outcome prediction, and targeted therapy utilization. The insights presented aim to inform future research directions and clinical practices in this field.

Recent findings

High risk neuroblastoma, comprising approximately 50% of all cases, presents a particularly poor prognosis. In 2008, the discovery of ALK aberrations in neuroblastoma marked a significant breakthrough, leading to the recognition of ALK as a target for tumors with activating ALK alterations. This discovery has paved the way for the development of various ALK inhibitors, which have shown promising clinical efficacy. ALK amplification, often observed alongside MYCN amplification, has been associated with unfavorable outcomes in patients. Activating mutations in the kinase domain of ALK, particularly at hotspot positions F1174, R1275, and F1245, have been identified. These mutations can occur at clonal or subclonal levels, posing challenges for early detection and potentially influencing disease progression and therapy resistance. The availability of ALK inhibitors, initially developed for adult cancers, has expedited the translation of this knowledge into targeted therapies for neuroblastoma. However, resistance to ALK inhibitors can emerge as a result of treatment or preexist as subclones within the tumor prior to therapy.

Summary

Future trials should focus on identifying additional targets complementing ALK inhibition to enhance treatment efficacy and overcome acquired resistance. Furthermore, the utilization of circulating tumor DNA as a non-invasive approach for longitudinal monitoring of ALK-positive neuroblastoma patients, in combination with radiographic evaluation of treatment response, holds promise for understanding dynamic tumor changes over time.

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Title: 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL
Authors: Salma Elmenawi
Mohamed Fawzy
Publication date: 11-03-2025
Publisher: Springer US
Keywords: Neuroblastoma
Neuroblastoma
Crizotinib
Lorlatinib
Published in: Current Oncology Reports
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-025-01650-w

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15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL

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Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma