Abstract
Aromatase inhibitors (AIs) are first-line treatment for ER+ breast cancer. However, despite responses initially, some patients can eventually acquire resistance. Moreover, 25% of all breast cancer patients do not express the estrogen receptor (ERα) and are innately resistance. In tumors of mouse models with acquired AI letrozole resistance, expression of ERα was reduced whereas HER2/growth factor signaling was enhanced. Treatment of mice with trastuzumab (HER2 antibody) reduced HER2/p-MAPK but restored ERα expression. The addition of trastuzumab to letrozole treatment when tumors progressed resulted in significantly longer tumor suppression than these drugs alone. Thus, inhibition of both HER2 and ERα signaling pathways was necessary to overcome resistance. In ERα-negative tumors, the receptor has been shown to be silenced by epigenetic modifications. Treatment of MDA-MB-231 ER-negative tumors with a histone deacetylase inhibitor, entinostat (ENT) increased expression of ERα and also aromatase. When ENT was combined with letrozole, tumor growth rate was markedly reduced compared with control tumors. ENT plus letrozole treatment also prevented the colonization and growth of MDA-MB-231 cells in the lung with significant reduction in visible and microscopic foci. These novel strategies could improve treatment for patients with acquired and innate resistance to AIs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.