Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer DOI Open Access
Donatella Romaniello,

Alessandra Morselli,

Ilaria Marrocco

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2957 - 2957

Published: March 25, 2025

Non-small-cell lung cancer (NSCLC) represents the most common type of cancer. The majority patients with characterized by activating mutations in epidermal growth factor receptor (EGFR), benefit from therapies entailing tyrosine kinase inhibitors (TKIs). In this regard, osimertinib, a third-generation EGFR TKI, has greatly improved outcome for EGFR-mutated AURA and FLAURA trials displayed superiority TKI both first- second-line settings, making it drug choice treating Unfortunately, onset resistance is almost inevitable. On-target mechanisms include new (e.g., C797S) domain EGFR, while among off-target mechanisms, amplification MET or HER2, downstream signaling molecules, oncogenic fusions, phenotypic changes EMT) have been described. This review focuses on strategies that are currently being investigated, preclinical clinical to overcome including use fourth-generation TKIs, PROTACs, bispecific antibodies, ADCs, as monotherapy part combination therapies.

Language: Английский

Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer DOI Open Access
Donatella Romaniello,

Alessandra Morselli,

Ilaria Marrocco

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2957 - 2957

Published: March 25, 2025

Non-small-cell lung cancer (NSCLC) represents the most common type of cancer. The majority patients with characterized by activating mutations in epidermal growth factor receptor (EGFR), benefit from therapies entailing tyrosine kinase inhibitors (TKIs). In this regard, osimertinib, a third-generation EGFR TKI, has greatly improved outcome for EGFR-mutated AURA and FLAURA trials displayed superiority TKI both first- second-line settings, making it drug choice treating Unfortunately, onset resistance is almost inevitable. On-target mechanisms include new (e.g., C797S) domain EGFR, while among off-target mechanisms, amplification MET or HER2, downstream signaling molecules, oncogenic fusions, phenotypic changes EMT) have been described. This review focuses on strategies that are currently being investigated, preclinical clinical to overcome including use fourth-generation TKIs, PROTACs, bispecific antibodies, ADCs, as monotherapy part combination therapies.

Language: Английский

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