Article
Endocrinology & Metabolism
Partha Das, Aritra Gupta, Kartiki V. Desai
Summary: High expression of JMJD6 is associated with poor prognosis and resistance to endocrine therapy in ER+ breast cancer. JMJD6 upregulates genes related to cell proliferation and downregulates ER target genes. Blocking ER alone may not eliminate proliferation of JMJD6-expressing ER+ cells. Immunostaining for JMJD6 could be developed as a potential marker for predicting endocrine therapy resistance.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Emily K. Zboril, Jacqueline M. Grible, David C. Boyd, Nicole S. Hairr, Tess J. Leftwich, Madelyn F. Esquivel, Alex K. Duong, Scott A. Turner, Andrea Ferreira-Gonzalez, Amy L. Olex, Carol A. Sartorius, Mikhail G. Dozmorov, J. Chuck Harrell
Summary: Breast cancer alone accounts for the majority of cancer deaths among women, with the most commonly diagnosed subtype being estrogen receptor positive (ER+). Survival has greatly improved for patients with ER+ breast cancer, due in part to the development of antiestrogen compounds, such as tamoxifen. While treatment of the primary disease is often successful, as many as 30% of patients will experience recurrence and metastasis, mainly due to developed endocrine therapy resistance. In this study, we discovered two tamoxifen combination therapies, with simeprevir and VX-680, that reduce the tumor burden in animal models of ER+ breast cancer more than either compound or tamoxifen alone. Additionally, these tamoxifen combinations reduced the expression of HER2, a hallmark of tamoxifen treatment, which can facilitate acquisition of a treatment-resistant phenotype. These combinations could provide clinical benefit by potentiating tamoxifen treatment in ER+ breast cancer.
Article
Biochemistry & Molecular Biology
Alok Mishra, Anshuman Srivastava, Ankit Pateriya, Manendra Singh Tomar, Anand Kumar Mishra, Ashutosh Shrivastava
Summary: Breast cancer is the most common cancer among females, and endocrine therapy for ER-positive breast cancer can result in acquired resistance. The metabolic state of cancer cells plays a crucial role in their susceptibility to chemotherapeutic drugs, and understanding metabolic pathway alterations in TAMR cancer may offer potential therapeutic strategies.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Oncology
Charles Dai, Leif W. Ellisen
Summary: Aberrant estrogen receptor (ER) signaling plays a key role in the development of many breast cancers. The androgen receptor (AR), similar to ER, is frequently expressed in breast cancer and has been considered as a potential therapeutic target. However, the understanding of androgen signaling in breast cancer is incomplete and there are conflicting findings regarding the role of AR. This article summarizes the current understanding of AR biology and recent investigations into AR-directed therapies in breast cancer.
Article
Medicine, Research & Experimental
Lei Wang, Jia Yi, Ling-yun Lu, Yue-ying Zhang, Lan Wang, Guo-sheng Hu, Yi-chen Liu, Jian-cheng Ding, Hai-feng Shen, Fang-qing Zhao, Hai-hua Huang, Wen Liu
Summary: The study revealed that estrogen can induce a circRNA program, with circPGR playing a crucial role in ER-positive breast cancer cell growth and tumorigenesis by acting as a ceRNA for miR-301a-5p to regulate cell cycle genes.
Article
Pharmacology & Pharmacy
Faten Shehadeh-Tout, Heloisa H. Milioli, Suraya Roslan, Patric J. Jansson, Mahendiran Dharmasivam, Dinny Graham, Robin Anderson, Tharushi Wijesinghe, Mahan Gholam Azad, Des R. Richardson, Zaklina Kovacevic
Summary: This study investigates a new class of anti-cancer agents for the treatment of ER-positive breast cancer. These agents inhibit multiple growth factor receptors and down-stream signaling, leading to decreased expression of hormone receptors and key resistance pathways. In vivo experiments demonstrate that these agents effectively inhibit ER-positive breast cancer growth. This represents an innovative non-hormonal, multi-modal therapeutic approach.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Akshay Sharma, Gatha Thacker, Mukul Mishra, Anil Kumar Singh, Vishal Upadhyay, Sabyasachi Sanyal, Arun Kumar Trivedi
Summary: In this study, we found that SOX4 positively regulates FBW7 expression at the transcriptional level by binding to the FBW7 promoter. We also observed a positive correlation between SOX4 and FBW7 mRNA levels in ER+ breast cancer cell lines and patient samples. Our findings suggest that increased levels of SOX4 and FBW7 promote cancer stemness and tumor cell dormancy. Additionally, the upregulation of SOX4 enhances FBW7-mediated degradation of GATA3, leading to tamoxifen resistance.
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Hasan Al-Kelabi, Dunya Al-Duhaidahawi, Khattab Al-Khafaji, Najim A. Al-Masoudi
Summary: A new class of tamoxifen analogues was synthesized using McMurry reaction conditions. The analogues showed potent activity against MCF-7 breast cancer cells, with compound 10 exhibiting the highest activity against aromatase. Docking studies showed that the new compounds had good correlations with experimental IC50, suggesting their potential as starting scaffolds for designing efficient drugs against estrogen receptor and aromatase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Pauliina M. Munne, Lahja Martikainen, Iiris Raty, Kia Bertula, Nonappa, Janika Ruuska, Hanna Ala-Hongisto, Aino Peura, Babette Hollmann, Lilya Euro, Kerim Yavuz, Linda Patrikainen, Maria Salmela, Juho Pokki, Mikko Kivento, Juho Vaananen, Tomi Suomi, Liina Nevalaita, Minna Mutka, Panu Kovanen, Marjut Leidenius, Tuomo Meretoja, Katja Hukkinen, Outi Monni, Jeroen Pouwels, Biswajyoti Sahu, Johanna Mattson, Heikki Joensuu, Paivi Heikkila, Laura L. Elo, Ciara Metcalfe, Melissa R. Junttila, Olli Ikkala, Juha Klefstrom
Summary: Researchers found that matrix stiffness regulates ERα expression via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation, revealing a crucial mechanobiological component in hormonal signaling in breast tissue.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Nivida Shete, Jordan Calabrese, Debra A. Tonetti
Summary: Estrogen is a key driver of estrogen-receptor-positive breast cancers, and drugs that block estrogen signaling are commonly used for treatment. Surprisingly, estrogen was previously used to treat breast cancer before the introduction of tamoxifen. This review focuses on the insights, molecular mechanisms, and potential clinical application of this counterintuitive therapeutic approach.
Article
Pharmacology & Pharmacy
Fatemeh Mahboobifard, Leila Dargahi, Masoumeh Jorjani, Fahimeh Ramezani Tehrani, Mohammad H. Pourgholami
Summary: ER alpha 36, a newly identified isoform of estrogen receptor, is highly expressed in the CNS and plays a role in neuroprotection, as well as maintaining bone density in postmenopausal women. Despite being considered an oncogenic molecule, ER alpha 36 paradoxically may have a protective role in certain tumors according to some studies.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Chih-Jung Chen, Ting-Hao Chen, Jason Lei, Ji-An Liang, Po-Sheng Yang, Chiun-Sheng Huang, Chia-Ming Hsieh, Ling-Ming Tseng, Liang-Chih Liu, Skye Hung-Chen Cheng, Kuan-Hui Shih
Summary: This study compared the biomarker expression and breast cancer subtyping results obtained by immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed concordance between the two methods, and RT-PCR performed similarly to IHC in predicting 5-year survival.
BIOSCIENCE REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Xue Chen, Jian-cheng Ding, Guo-sheng Hu, Xing-yi Shu, Yan Liu, Jun Du, Zi-jing Wen, Jun-yi Liu, Hai-hua Huang, Guo-hui Tang, Wen Liu
Summary: This study identifies a highly expressed estrogen-induced lncRNA, LINC02568, in ER-positive breast cancer, which plays important roles in cell growth, tumorigenesis, and endocrine therapy drug resistance. Mechanistically, LINC02568 regulates estrogen/ERα-induced gene transcriptional activation by stabilizing ESR1 mRNA through sponging miR-1233-5p in the cytoplasm. Additionally, LINC02568 contributes to tumor-specific pH homeostasis by regulating carbonic anhydrase CA12 in the nucleus. The dual functions of LINC02568 contribute to breast cancer progression and drug resistance.
Article
Biochemistry & Molecular Biology
Shaimaa Hamza, Ekaterina E. E. Garanina, Mohammad Alsaadi, Svetlana F. F. Khaiboullina, Gulcin Tezcan
Summary: NLRP3 may contribute to the growth and propagation of breast cancer, and the effects of ER-alpha, PR, and HER2 on NLRP3 activation in breast cancer are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Cara C. Schafer, Yong Wang, Kenneth P. Hough, Anandi Sawant, Stefan C. Grant, Victor J. Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S. Deshane
Article
Immunology
Yong Wang, Cara C. Schafer, Kenneth P. Hough, Sultan Tousif, Steven R. Duncan, John F. Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S. Deshane
JOURNAL OF IMMUNOLOGY
(2018)
Article
Oncology
Anandi Sawant, Cara C. Schafer, Tong Huan Jin, Jaroslaw Zmijewski, Hubert M. Tse, Justin Roth, Zhihuan Sun, Gene P. Siegal, Victor J. Thannickal, Stefan C. Grant, Selvarangan Ponnazhagan, Jessy S. Deshane
Editorial Material
Oncology
Anandi Sawant, Cara C. Schafer, Selvarangan Ponnazhagan, Jessy S. Deshane
Article
Multidisciplinary Sciences
William Gesztes, Cara Schafer, Denise Young, Jesse Fox, Jiji Jiang, Yongmei Chen, Huai-Ching Kuo, Kuwong B. Mwamukonda, Albert Dobi, Allen P. Burke, Judd W. Moul, David G. McLeod, Inger L. Rosner, Gyorgy Petrovics, Shyh-Han Tan, Jennifer Cullen, Shiv Srivastava, Isabell A. Sesterhenn
Summary: TP53 is frequently mutated in prostate cancer and its immunohistochemical assessment can improve prognosis. This study evaluated p53 protein expression and lymphovascular invasion (LVI) by immunohistochemistry in prostate cancer patients and found that both factors were associated with metastatic progression. The study also detected TP53 mutations in tumors with high p53 expression and suggested that high levels of p53 expression and the presence of LVI could enhance the early prediction of prostate cancer progression.
SCIENTIFIC REPORTS
(2022)