Nat commun: researchers reveal the root cause of drug resistance in some lung cancers

February 28, 2019 / Biovalley / researchers from Kanazawa University published a new study in nature communications, which showed that Axl (a member of the tyrosine kinase receptor family) can cause some lung cancer patients to have inherent resistance to ocitinib, and combination of ocitinib and Axl inhibitors can significantly reduce the resistance of cancer cells to ocitinib Photo source: nature communications often uses drugs based on tyrosine kinase inhibitors in the treatment of cancer, one of which is called ocitinib, which has been approved for the treatment of lung cancer with EGFR mutation and has certain curative effect However, some patients are naturally resistant to ocitinib, so their response to the drug is poor Seiji Yano and colleagues from the University of Kanazawa now find that Axl causes cancer cells that are resistant to ocitinib, which leads to the resistance of lung cancer to ocitinib The researchers first found that ositinib activated Axl in EGFR mutant lung cancer cells in vitro, and then they found that Axl activity was inversely related to the sensitivity of cells to tyrosine kinase inhibitors Axl expression was related to patients' poor response to ositinib and early recurrence Yano and his colleagues tested whether the drug-resistant cells overexpressed Axl It was found that the survival rate of drug-resistant cells could be reduced by using Axl inhibitor nps1034 at the same time The researchers then looked at the efficacy of Axl inhibitors in combination with ocitinib in the treatment of mice tumors Nps1034 alone has no antitumor effect Only using oxitinib can make the tumor subside, but the tumor will grow again within 7 weeks At the same time, the use of inhibitors and ocitinib can make the tumor stop growing within one week, and the tumor size is stable within 10 weeks No serious side effects were observed during the treatment This finding provides an important molecular mechanism for revealing the tolerance of EGFR mutant lung cancer cells to ocitinib, especially the role of Axl and its inhibitory effect The authors say these results suggest that combination of ositinib and Axl inhibitors may prevent cancer cells from developing resistance to ositinib in the early stages of treatment Reference: Hirokazu Taniguchi et al, Axl confers intrinsic resistance to positinib and advances the energy of toalerant cells, nature communications (2019) Doi: 10.1038/s41467-018-08074-0