Research ArticleCancer therapy

ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells

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Science Signaling  17 Nov 2020:
Vol. 13, Issue 658, eabb9820
DOI: 10.1126/scisignal.abb9820

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Unmasking drug sensitivity

Although the activity of the epidermal growth factor receptor (EGFR) pathway is increased in triple-negative breast cancers (TNBC), patients are generally insensitive to EGFR inhibitors. Cruz-Gordillo et al. found that this is because TNBC cells produced the prosurvival protein Mcl-1. A gene deletion screen revealed that insensitivity to the EGFR inhibitor erlotinib required MCL1 expression promoted by the ELP family of transcription-elongation regulators, particularly ELP4. The findings suggest that an ELP4–Mcl-1 mechanism masks erlotinib sensitivity in TNBC and that combining erlotinib with an Mcl-1 inhibitor might be effective in patients with TNBC.

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