AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells
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.
- Nature Communications 10, 259 (2019). doi: 10.1038/s41467-018-08074-0
|Kanazawa University (KU), Japan||0.33|
|Kyoto Prefectural University of Medicine (KPUM), Japan||0.19|
|Nagasaki University, Japan||0.10|
|National Cancer Institute (INCA), Brazil||0.08|
|Niigata University, Japan||0.08|
|Niigata Cancer Center Hospital, Japan||0.08|
|Kyoto First Red Cross Hospital, Japan||0.04|
|Japanese Red Cross Society, Japan||0.04|
|Tokushima University, Japan||0.04|