AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

Journal: Nature Communications

Published: 2019-01-16

DOI: 10.1038/s41467-018-08074-0

Affiliations: 12

Authors: 24

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Research Highlight

Tackling drug resistance in lung cancer

© BSIP/Getty

© BSIP/Getty

A Kanazawa University–led team has discovered why some patients with lung cancer develop resistance to osimertinib, a potent and selective drug inhibitor of a protein called EGFR.

The researchers showed that osimertinib can stimulate AXL, a surface receptor found on cancer cells, and that activation of this protein makes cells more tolerant to the drug.

In patient samples, lung tumours with high expression of AXL tended to have lower response rates to EGFR-targeted drugs. And in mice, combined treatment of an AXL inhibitor together with osimertinib led to more prolonged tumour regression than treatment with either agent alone.

The team propose trying a similar strategy in patients to prevent the development of drug resistance to osimertinib — and indeed just such a combination trial is currently ongoing in Taiwan.

Supported content

  1. Nature Communications 10, 259 (2019). doi: 10.1038/s41467-018-08074-0
Institutions Share
Division of Medical Oncology, KU, Japan 0.27
Graduate School of Medical Sciences, KPUM, Japan 0.19
Graduate School of Biomedical Sciences, Nagasaki University, Japan 0.10
National Cancer Institute (INCA), Brazil 0.08
Graduate School of Medical and Dental Science (MDS), Niigata University, Japan 0.08
Niigata Cancer Center Hospital, Japan 0.08
Kyoto First Red Cross Hospital, Japan 0.04
Division of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Japan 0.04
Japanese Red Cross Nagasaki Atomic Bomb Hospital, Japan 0.04
Graduate School of Biomedical Sciences, Tokushima University, Japan 0.04
WPI Nano Life Science Institute (NanoLSI), KU, Japan 0.02

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