Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer

dc.contributor.authorKhatpe, Aditi S.
dc.contributor.authorAdebayo, Adedeji K.
dc.contributor.authorHerodotou, Christopher A.
dc.contributor.authorKumar, Brijesh
dc.contributor.authorNakshatri, Harikrishna
dc.contributor.departmentSurgery, School of Medicineen_US
dc.date.accessioned2022-05-12T15:23:06Z
dc.date.available2022-05-12T15:23:06Z
dc.date.issued2021-01-20
dc.description.abstractSignaling from estrogen receptor alpha (ERα) and its ligand estradiol (E2) is critical for growth of ≈70% of breast cancers. Therefore, several drugs that inhibit ERα functions have been in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ERα+ breast cancers respond to anti-estrogen therapy, ≈30% of these breast cancers recur, sometimes even after 20 years of initial diagnosis. Mechanism of resistance to anti-estrogens is one of the intensely studied disciplines in breast cancer. Several mechanisms have been proposed including mutations in ESR1, crosstalk between growth factor and ERα signaling, and interplay between cell cycle machinery and ERα signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ERα thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERα. As a result of these studies, several therapies that combine anti-estrogens that degrade ERα with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ERα+ breast cancers. In this review, we discuss the nexus between ERα-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationKhatpe AS, Adebayo AK, Herodotou CA, Kumar B, Nakshatri H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers (Basel). 2021;13(3):369. Published 2021 Jan 20. doi:10.3390/cancers13030369en_US
dc.identifier.urihttps://hdl.handle.net/1805/28963
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/cancers13030369en_US
dc.relation.journalCancersen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0*
dc.sourcePMCen_US
dc.subjectAnti-estrogen resistanceen_US
dc.subjectBreast canceren_US
dc.subjectEstrogen receptoren_US
dc.titleNexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Canceren_US
dc.typeArticleen_US
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