Circulating tumor DNA landscape and prognostic impact of acquired resistance to targeted therapies in cancer patients: a national center for precision medicine (PRISM) study

Arnaud Bayle, Laila Belcaid, Lola Jade Palmieri, Diego Teysonneau, Sophie Cousin, Mariella Spalato-Ceruso, Mihaela Aldea, Damien Vasseur, Melissa Alame, Laura Blouin, Isabelle Soubeyran, Claudio Nicotra, Maud Ngocamus, Antoine Hollebecque, Yohann Loriot, Benjamin Besse, Ludovic Lacroix, Etienne Rouleau, Fabrice Barlesi, Fabrice AndreAntoine Italiano

    Résultats de recherche: Contribution à un journalLetterRevue par des pairs

    4 Citations (Scopus)

    Résumé

    Background: Despite the effectiveness of the various targeted therapies currently approved for solid tumors, acquired resistance remains a persistent problem that limits the ultimate effectiveness of these treatments. Polyclonal resistance to targeted therapy has been described in multiple solid tumors through high-throughput analysis of multiple tumor tissue samples from a single patient. However, biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient. Methods: We analyzed circulating tumor DNA (ctDNA) with a large next-generation sequencing panel to characterize the landscape of secondary resistance mechanisms in two independent prospective cohorts of patients (STING: n = 626; BIP: n = 437) with solid tumors who were treated with various types of targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies and hormonal therapies. Results: Emerging alterations involved in secondary resistance were observed in the plasma of up 34% of patients regardless of the type of targeted therapy. Alterations were polyclonal in up to 14% of patients. Emerging ctDNA alterations were associated with significantly shorter overall survival for patients with some tumor types. Conclusion: This comprehensive landscape of genomic aberrations indicates that genetic alterations involved in secondary resistance to targeted therapy occur frequently and suggests that the detection of such alterations before disease progression may guide personalized treatment and improve patient outcome.

    langue originaleAnglais
    Numéro d'article176
    journalMolecular Cancer
    Volume22
    Numéro de publication1
    Les DOIs
    étatPublié - 1 déc. 2023

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