Cancer letters

Combining osimertinib with AXL and FGFR blockers improves treatment of EGFR-mutated lung cancer

Updated

Abstract

Triple therapy with osimertinib, ONO-7475, and FGFR inhibitor BGJ398 significantly increased apoptosis in high-AXL-expressing EGFR-mutated non-small cell lung cancer cells.

  • FGFR1 knockdown showed strong inhibition of cell growth when combined with osimertinib and ONO-7475.
  • Increased expression of the pro-apoptotic factor Bim was observed with the triple therapy.
  • Cell viability was reduced significantly with the addition of the FGFR inhibitor BGJ398 compared to the dual therapy.
  • Xenograft models demonstrated that the triple therapy effectively suppressed tumor regrowth.
  • Initial FGFR1 inhibition may help prevent the development of resistance to osimertinib and ONO-7475.

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Full Text

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Funding

Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. Yamada received commercial research grants from Ono Pharmaceutical, Janssen Pharmaceutical K.K., AstraZeneca, and Takeda Pharmaceutical Company Limited and speaking honoraria from Eli Lilly and Chugai-Roche. H. Kawachi received personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Eli Lilly Japan, and MSD outside the purview of the submitted work. A. Osoegawa received consultant honoraria from AstraZeneca and speaking honoraria from AstraZeneca, MSD Japan, Chugai Pharmaceutical, Bristol Myers Squibb, and Ono Pharmaceutical. T. Sakai received research grants from Otsuka Pharmaceutical, Taiho Pharmaceutical, and Oncolys BioPharma and a patent fee from JT Pharmaceutical. T. Yasuhiro and R. Kozaki are paid employees of Ono Pharmaceutical. S. Yano received research grants from Chugai-Roche and Boehringer-Ingelheim and speaking honoraria from Amgen, Chugai-Roche, Boehringer-Ingelheim, Novartis, and Pfizer. K. Takayama received research grants from Chugai-Roche and Ono Pharmaceutical and personal fees from AstraZeneca, Chugai-Roche, MSD-Merck, Eli Lilly, Boehringer-Ingelheim, and Daiichi-Sankyo. The other authors have no conflicts of interest to declare.
PubMed

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