Fiche publication
Date publication
décembre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEAU-FALLER Michèle
Tous les auteurs :
Cadranel J, Ruppert AM, Beau-Faller M, Wislez M
Lien Pubmed
Résumé
Activating mutation in exons 19 or 21 of epidermal growth factor receptor (EGFR) in non-small-cell lung cancers (NSCLC) are associated with increased sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib. Cancer patients harboring activating EGFR mutations benefit from first-line TKI therapy. Yet 10% of patients present a primary TKI resistance, while 50% of the others develop a secondary resistance within 9-12 months after starting TKI. The RECIST's definition of progression appears flawed when applied to EGFR-mutated NSCLC patients. Most often, tumor volume shrinking widely exceeds 30% during TKI response and kinetics of growth is low during relapse. At present, secondary resistance mechanisms associated with progression are better known: clonal selection of EGFR resistance mutation (T790M mutation in exon 20), amplification of transmembrane receptors for other growth factors (c-met, HER family, IGF1R, or AXL), downstream molecular alterations in EGFR signaling pathway (PI3K or PTEN), and epithelial-mesenchymal transition or transdifferentiation to small-cell cancer. The best strategy for secondary resistance is not well-defined: maintaining TKI therapy, switching to chemotherapy, combining both treatments, or using new therapies targeting other signaling pathways.
Référence
Crit Rev Oncol Hematol. 2013 Dec;88(3):477-93
