摘要
Breast cancer is the most prevalent malignancy that affects women worldwide,with approximately 70%of cases classified as hormone receptor-positive(HR+).Endocrine therapy is one of the principal treatment modalities for this patient cohort.However,a considerable proportion of tumors acquire resistance to endocrine therapeutics,resulting in reduced effectiveness as the disease progresses,but the underlying mechanisms are not fully characterized.The G protein-coupled estrogen receptor(GPER),a component of the G proteincoupled receptor family,is hypothesized to mediate estrogenic effects independently of conventional estrogen receptors.In recent years,our research group and others have demonstrated that GPER plays a crucial role in facilitating the clinical progression of HR+breast cancer and significantly contributes to endocrine resistance.In this review,we summarize the diverse mechanisms through which GPER mediates endocrine resistance,encompassing somatic alterations,epigenetic and non-genetic variations,and modifications within the tumor microenvironment.Furthermore,we discuss GPER as a potential therapeutic target for overcoming endocrine resistance of HR+breast cancer in future clinical applications.
基金
supported in part by research grants from the National Natural Science Foundation of China(No.82160565,82260565,82104289)
the Jiangxi Province Ganpo Talent Support Program(China)(No.20232BCJ23035)
the Youths Program of the Natural Science Foundation of Jiangxi Province,China(No.20212BAB216063)
the Science and Technology Research Project of Jiangxi Provincial Department of Education(China)(No.GJJ2203530)
the Research Open Fund Project of Jiangxi Cancer Hospital(China)(No.KFJJ2023ZD01,KFJJ2023YB06)
the Shandong Provincial Health Commission of China(No.M-2022053)
the Science and Technology Innovation Plan from Weifang Medical University(Shandong,China)(No.041004)
the Yuandu Scholar Grant of Weifang City,Weifang Science and Technology Bureau Plan Project(Shandong,China)(No.2021YX081)
the Science and technology project jointly established by the Science and Technology Department of the State Administration of Traditional Chinese Medicine(China)(No.GZYKJS-SD-2023-079)
the Shandong Provincial Medical Association Young Talent Promotion Project(China)(No.2023_GJ_0039)
the Science and Technology Innovation Plan from Weifang Medical University(Shandong,China)(No.041011)
the US National Institutes of Health(No.CA226303 to T.C.H.,DE030480 to R.R.R.)
supported by the Mabel Green Myers Research Endowment Fund
The University of Chicago Orthopaedics Alumni Fund.
