EGFR amplification confers resistance to third-generation EGFR-TKIs which can be overcome by HSP90 inhibition. The results provide a preclinical rationale for the use of HSP90 inhibitors to overcome EGFR amplification-mediated resistance.

over 3 years ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR T790M • EGFR amplification • EGFR overexpression

Tagrisso (osimertinib) • TAS-121

4years

TAS-121, a selective mutant EGFR inhibitor, shows activity against tumors expressing various EGFR mutations including T790M and uncommon mutations G719X. (PubMed, Mol Cancer Ther)

TAS-121 potently inhibited common activating and resistance EGFR mutations to the same extent as another third-generation EGFR-TKI (osimertinib). Moreover, TAS-121 displayed antitumor activity in SW48 (EGFR G719S) and NCI-H1975 (EGFR L858R/T790M) xenograft models, and achieved an objective response in NSCLC patients with EGFR mutations including G719A mutation. In conclusion, TAS-121 is a novel third-generation EGFR-TKI and demonstrates anti-tumor activities in patients with NSCLC expressing either common or uncommon EGFR mutations.

4 years ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR T790M • EGFR expression • EGFR L861Q • EGFR G719X • EGFR G719A • EGFR G719S

Tagrisso (osimertinib) • TAS-121