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. 2021 Jul 6;9:692173. doi: 10.3389/fcell.2021.692173

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Copyright © 2021 Edwards and Brennan.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Notch inhibition may be a viable strategy for targeting therapy resistant breast cancer cells. ER and HER2 signalling inhibits Notch in ER+ and HER2+ breast cancer cells respectively. Endocrine or trastuzumab treatment inhibit these pathways, releasing the blockade on Notch signalling. Pro-survival Notch activity enables the cells to survive the targeted treatments. Notch inhibitors could be used in combination to sensitise these resistant cells to the targeted treatment. Triple negative breast cancer cells lack the ER and HER2 receptors, meaning that they are unaffected by endocrine therapy or trastuzumab, but are sensitive to Notch inhibitors.