ALK fusions turn sixteen in lung cancer: a review on their biology, detection and therapy

Francesco Facchinetti, Laura Gandolfi, Damien Vasseur, Laura Melocchi, Seshiru Nakazawa, Marcello Tiseo, Luc Friboulet, Giulio Rossi

    Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

    1 Citation (Scopus)

    Résumé

    During the last two decades, the field of targeted therapy against oncogene-driven tumors has witnessed meaningful and accelerated advancements. Ever since the discovery of ALK (anaplastic lymphoma kinase) rearrangements as driver events for non-small cell lung cancer (NSCLC) in 2007, targeting ALK has become a model of precision oncology. Especially, the recognition of crizotinib as an active and effective tyrosine kinase inhibitor (TKI) for ALK-positive NSCLC defined the proof-of-concept that ALK inhibition had important clinical value. Furthermore, a better understanding of crizotinib liabilities and resistance mechanisms prompted the development of the next generations of ALK inhibitors, leading to a shift in treatment strategy, from a sequential approach to a “new generation agents upfront” one. The continuous interrogation of resistance mechanisms to the novel inhibitors is the key feature to improving patients’ outcomes through the development of novel treatment strategies. From this perspective, the evolution of ALK inhibition in NSCLC could be defined as a cornerstone for the clinical improvements achievable in patients suffering from oncogene-driven tumors. In this review, we approach the entity of ALK fusions in lung cancer reporting the mechanisms conferring oncogenic competence, and describing the molecular diagnostic tools to detect them in the clinical practice. We then report how new generations of ALK TKIs are developed in a continuous effort to overcome the resistance to previous agents, and how these novel drugs have shaped the current therapeutic landscape for patients with ALK-positive lung cancer.

    langue originaleAnglais
    Numéro d'article2
    journalPrecision Cancer Medicine
    Volume6
    Les DOIs
    étatPublié - 30 sept. 2024

    Contient cette citation