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      Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer

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          Abstract

          Drug resistance is always a great obstacle in any endocrine therapy of breast cancer. Although the combination of endocrine therapy and targeted therapy has been shown to significantly improve prognosis, refractory endocrine resistance is still common. Dysregulation of the Hippo pathway is often related to the occurrence and the development of many tumors. Targeted therapies of this pathway have played important roles in the study of triple negative breast cancer (TNBC). Targeting the Hippo pathway in combination with chemotherapy or other targeted therapies has been shown to significantly improve specific antitumor effects and reduce cancer antidrug resistance. Further exploration has shown that the Hippo pathway is closely related to endocrine resistance, and it plays a “co-correlation point” role in numerous pathways involving endocrine resistance, including related pathways in breast cancer stem cells (BCSCs). Agents and miRNAs targeting the components of the Hippo pathway are expected to significantly enhance the sensitivity of breast cancer cells to endocrine therapy. This review initially explains the possible mechanism of the Hippo pathway in combating endocrine resistance, and it concludes by recommending endocrine therapy in combination with therapies targeting the Hippo pathway in the study of endocrine-resistant breast cancers.

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          Most cited references152

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

            PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The PI3Kα-specific inhibitor alpelisib has shown antitumor activity in early studies.
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              YAP/TAZ at the Roots of Cancer.

              YAP and TAZ are highly related transcriptional regulators pervasively activated in human malignancies. Recent work indicates that, remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, chemoresistance, and metastasis. YAP/TAZ are sensors of the structural and mechanical features of the cell microenvironment. A number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway. Addiction to YAP/TAZ thus potentially represents a central cancer vulnerability that may be exploited therapeutically.
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                Author and article information

                Contributors
                alexandertobiasteichmann@swmu.edu.cn
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                10 June 2021
                10 June 2021
                2021
                : 21
                : 306
                Affiliations
                [1 ]GRID grid.488387.8, Department of Gynaecology and Obstetrics, , The Affiliated Hospital of Southwest Medical University, ; No. 25 Taiping Street, Jiangyang District, Luzhou, 646000 People’s Republic of China
                [2 ]GRID grid.488387.8, Sichuan Provincial Center for Gynaecology and Breast Diseases, , The Affiliated Hospital of Southwest Medical University, ; Luzhou, 646000 China
                [3 ]GRID grid.449525.b, ISNI 0000 0004 1798 4472, North Sichuan Medical College, ; Nanchong, 637000 China
                [4 ]GRID grid.460059.e, Department of Gynaecology, , The Second People’s Hospital of Yibin, ; Yibin, 644000 China
                Author information
                http://orcid.org/0000-0002-3753-129X
                Article
                1999
                10.1186/s12935-021-01999-5
                8194146
                34112175
                2869c1ab-6717-4ba0-8c84-caa44680f273
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 March 2021
                : 27 May 2021
                Funding
                Funded by: Luzhou City
                Award ID: 02-00040055
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                hippo pathway,breast cancer,endocrine therapy,endocrine resistance,breast cancer stem cells,microrna

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