Research ArticleCancer

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

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Science Signaling  29 Mar 2016:
Vol. 9, Issue 421, pp. ra33
DOI: 10.1126/scisignal.aac8460

Reversing resistance in lung cancer

Although initially effective in treating some non–small cell lung cancer (NSCLC) patients, resistance develops to targeted inhibitors of the tyrosine kinase receptor EGFR. Gao et al. found that inhibiting the kinase JAK2 can restore EGFR inhibitor sensitivity in NSCLC cells. JAK2 formed a complex with EGFR and the protein SOCS5, which promotes the internalization and degradation of receptors. In the absence of functional JAK2, less SOCS5 interacted with EGFR, which reduced the ubiquitin-mediated degradation of EGFR. The EGFRs remaining at the cell surface were heterodimers of mutant and wild-type receptors and were sensitive to EGFR inhibitors. Thus, combining JAK inhibitors with EGFR inhibitors may overcome drug resistance in NSCLC patients.

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