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Breast Cancer Res Treat 2021 Apr 15. Epub 2021 Apr 15.

Houston Methodist Cancer Center, Houston, TX, USA.

Introduction: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. Read More

Pathol Res Pract 2021 Apr 5;222:153430. Epub 2021 Apr 5.

Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia. Electronic address:

The Aim: of the study was to determine the clinical relevance of cyclin D1 (cD1) and its association with clinicopathological parameters in breast cancer patients treated with hormonal therapy.

Material And Methods: The study included 96 primary breast cancer patients with known clinicopathological parameters. In adjuvant setting, 44 patients were tamoxifen-treated and 52 were treated with ovarian irradiation/ablation. Read More

Biomed Res Int 2021 16;2021:6618519. Epub 2021 Mar 16.

Li Huili Hospital, Ningbo Medical Center, Ningbo 315040, China.

Objective: The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer.

Methods: The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Read More

Cells 2021 Mar 16;10(3). Epub 2021 Mar 16.

Cancer Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.

Molecular alterations in cancer genes and associated signaling pathways are used to inform new treatments for precision medicine in cancer. Small molecule inhibitors and monoclonal antibodies directed at relevant cancer-related proteins have been instrumental in delivering successful treatments of some blood malignancies (e.g. Read More

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.

Endocrine resistance is a major complication during treatment of estrogen receptor-positive breast cancer. Although autophagy has recently gained increasing consideration among the causative factors, the link between autophagy and endocrine resistance remains elusive. Here, we investigate the autophagy-based mechanisms of tamoxifen resistance in MCF7 cells. Read More

Cancers (Basel) 2021 Mar 25;13(7). Epub 2021 Mar 25.

Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Breast cancer is the most common female cancer. About 70% of breast cancer patients are estrogen receptor α (ERα) positive (ER+) with tamoxifen being the most commonly used anti-endocrine therapy. However, up to 50% of patients who receive tamoxifen suffer recurrence. Read More

J Pers Med 2021 Mar 13;11(3). Epub 2021 Mar 13.

Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.

Tamoxifen is an endocrine treatment for hormone receptor positive breast cancer. The effectiveness of tamoxifen may be compromised in patients with metabolic resistance, who have insufficient metabolic generation of the active metabolites endoxifen and 4-hydroxy-tamoxifen. This has been challenging to validate due to the lack of measured metabolite concentrations in tamoxifen clinical trials. Read More

Cancers (Basel) 2021 Mar 6;13(5). Epub 2021 Mar 6.

Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA.

The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. Read More

Pharmacol Res 2021 Mar 30;168:105585. Epub 2021 Mar 30.

University of Illinois at Chicago, College of Pharmacy, Department of Pharmaceutical Sciences, 833 South Wood Street, Chicago, IL 60612, USA. Electronic address:

Cancer is the second leading cause of death worldwide, and the World Health Organization estimates that one in six deaths globally is due to cancer. Chemotherapy is one of the major modalities used to treat advanced cancers and their metastasis. However, the existence of acquired and intrinsic resistance to anti-cancer drugs often diminishes their therapeutic effect. Read More

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211004935

Wuxi School of Medicine, Jiangnan University, Wuxi, People's Republic of China.

Fibroblast growth factor receptor 1 (FGFR1) is widely recognized as a key player in mammary carcinogenesis and associated with the prognosis and therapeutic response of breast cancers. With the aim of investigating the correlation between FGFR1 expression and estrogen receptor (ER) and exploring the effect of FGFR1 on endocrine therapy response and ER+ breast cancer prognosis, we examined the FGFR1 protein expression among 184 ER-positive breast cancers by the immunohistochemistry (IHC) method, analyzed the association between FGFR1 expression and disease characters using the Pearson's chi-square test, and assessed the prognostic role of FGFR1 among breast cancers using Cox regression and Kaplan-Meier analyses. Moreover, assays were conducted to confirm the correlation between FGFR1 and ER expression and investigate the effect of FGFR1 on tamoxifen (TAM) sensitivity in ER breast cancer. Read More

Front Oncol 2021 10;11:638751. Epub 2021 Mar 10.

Xinxiang Key Laboratory of Tumor Migration, Invasion and Precision Medicine, Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.

Background: Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Read More

Front Oncol 2021 11;11:617937. Epub 2021 Mar 11.

Laboratory of Immunobiology and Ionic Transport Regulation, University Center for Biomedical Research, University of Colima, Colima, Mexico.

Glucocorticoids (GCs) are a central component of multi-drug treatment protocols against T and B acute lymphoblastic leukemia (ALL), which are used intensively during the remission induction to rapidly eliminate the leukemic blasts. The primary response to GCs predicts the overall response to treatment and clinical outcome. In this review, we have critically analyzed the available data on the effects of GCs on sensitive and resistant leukemic cells, in order to reveal the mechanisms of GC resistance and how these mechanisms may determine a poor outcome in ALL. Read More

Cell Death Dis 2021 Mar 26;12(4):329. Epub 2021 Mar 26.

Affiliated Cancer Hospital & institute of Guangzhou Medical University, Guangzhou, 510095, China.

Breast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Read More

Transl Oncol 2021 Mar 21;14(6):101046. Epub 2021 Mar 21.

Department of Pharmacology, School of Pharmacy, Duquesne University, Pittsburgh, PA 15219, USA. Electronic address:

The epithelial to mesenchymal transition (EMT) is characterized by a loss of cell polarity, a decrease in the epithelial cell marker E-cadherin, and an increase in mesenchymal markers including the zinc-finger E-box binding homeobox (ZEB1). The EMT is also associated with an increase in cell migration and anchorage-independent growth. Induction of a reversal of the EMT, a mesenchymal to epithelial transition (MET), is an emerging strategy being explored to attenuate the metastatic potential of aggressive cancer types, such as triple-negative breast cancers (TNBCs) and tamoxifen-resistant (TAMR) ER-positive breast cancers, which have a mesenchymal phenotype. Read More

J Mol Cell Biol 2021 Mar 23. Epub 2021 Mar 23.

Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USA.

Tamoxifen (TAM) is the first-line endocrine therapy for estrogen receptor-positive (ER+) breast cancer (BC). However, acquired resistance occurs in ∼50% cases. Meanwhile, although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients, complex signaling feedback loops exist, which can counter the effectiveness of inhibitors of this pathway. Read More

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211004916

Tongchuan people's Hospital, Tongchuan, Shaanxi, China.

Background: Tamoxifen (TAM) is the eminent first-line drug for endocrine therapy of hormone receptor positive premenopausal breast cancer and reduces the risk of recurrence by ∼50%. However, many patients developed TAM resistance and their diseases recurred. Our previous study on transcriptome profile of TAM resistant breast cancer cells revealed that the TMEM47 is one of the most significantly differentially expressed genes. Read More

Ther Adv Med Oncol 2021 26;13:1758835921993436. Epub 2021 Feb 26.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510000, China.

Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR. Read More

Physiol Genomics 2021 Apr 15;53(4):150-159. Epub 2021 Mar 15.

Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

We have assessed the role of ric-b8 in the control of heart rate after the gene was implicated in a recent genome-wide association study of resting heart rate. We developed a novel murine model in which it was possible to conditionally delete ric-8b in the sinoatrial (SA) node after the addition of tamoxifen. Despite this, we were unable to obtain homozygotes and thus studied heterozygotes. Read More

Ann Transl Med 2021 Feb;9(3):258

Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.

Background: Tamoxifen is an important choice in endocrine therapy for patients with oestrogen receptor-positive (ER+) breast cancer, and disease progression-associated resistance to tamoxifen therapy is still challenging. Flap endonuclease-1 (FEN1) is used as a prognostic biomarker and is considered to participate in proliferation, migration, and drug resistance in multiple cancers, especially breast cancer, but the prognostic function of FEN1 in ER+ breast cancer, and whether FEN1 is related to tamoxifen resistance or not, remain to be explored.

Methods: On-line database Kaplan-Meier (KM) plotter, GEO datasets, and immunohistochemistry were used to analyse the prognostic value of FEN1 in ER+ breast cancer from mRNA and protein levels. Read More

Life Sci 2021 May 8;273:119307. Epub 2021 Mar 8.

The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, PR China; Gansu Academy of Traditional Chinese Medicine, Lanzhou City, Gansu Province, PR China. Electronic address:

Aims: The human epidermal growth factor receptor (HER) family gene is involved in a wide range of biological functions in human cancers. Nevertheless, there is little research that comprehensively analysis the correlation between HER family members and prognosis, tumor microenvironment (TME) in different cancers.

Materials And Methods: Based on updated public databases and integrated several bioinformatics analysis methods, we evaluated expression level, prognostic values of HER family gene and explore the association between expression of HER family gene and TME, Stemness score, immune subtype, drug sensitivity in pan-cancer. Read More

Oncogene 2021 Apr 8;40(14):2539-2552. Epub 2021 Mar 8.

Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague-West, Czech Republic.

Pancreatic cancer is one of the deadliest forms of cancer, which is attributed to lack of effective treatment options and drug resistance. Mitochondrial inhibitors have emerged as a promising class of anticancer drugs, and several inhibitors of the electron transport chain (ETC) are being clinically evaluated. We hypothesized that resistance to ETC inhibitors from the biguanide class could be induced by inactivation of SMAD4, an important tumor suppressor involved in transforming growth factor β (TGFβ) signaling, and associated with altered mitochondrial activity. Read More

Biomed Pharmacother 2021 Mar 3;138:111447. Epub 2021 Mar 3.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

H19 is an oncofetal transcript with crucial roles in the development and progression of several neoplastic cells. With anti-apoptotic, pro-proliferative, and pro-migratory functions, H19 affects the carcinogenic process from different functional points. In addition, H19 has central roles in the induction of chemoresistance in breast cancer, lung cancer, glioma, liver cancer, and other types of cancers. Read More

Integr Cancer Ther 2021 Jan-Dec;20:1534735421996822

Dongfang Hospital affiliated to Beijing University of Traditional Chinese Medicine, Beijing, China.

Background: Tamoxifen is one of the medicines for adjuvant endocrine therapy of hormone-dependent breast cancer. However, development of resistance to tamoxifen occurs inevitably during treatment. This study aimed to determine whether sensitivity of tamoxifen-resistant breast cancer cells (TAM-R) could be reinstated by tetrandrine (Tet). Read More

J Pathol 2021 Feb 27. Epub 2021 Feb 27.

Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, PR China.

Tamoxifen (TAM) resistance is a significant clinical challenge in endocrine therapies for estrogen receptor (ER)-positive breast cancer patients. Cullin 4B (CUL4B), which acts as a scaffold protein in CUL4B-RING ubiquitin ligase complexes (CRL4B), is frequently overexpressed in cancer and represses tumor suppressors through diverse epigenetic mechanisms. However, the role and the underlying mechanisms of CUL4B in regulating drug resistance remain unknown. Read More

Turk J Pharm Sci 2021 Feb;18(1):68-74

Karbala University College of Medicine, Department of Microbiology, Karbala, Iraq.

Objectives: Tamoxifen (TAM), which is used for treating breast cancer, has exhibited another important function as an antimicrobial agent. The objective of this study is to investigate the antibacterial action of TAM against the bacteria present in the human oral cavity.

Materials And Methods: The bacteria present in the human oral cavity were isolated from healthy individuals. Read More

Mol Cancer Res 2021 Feb 24. Epub 2021 Feb 24.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.

Despite the availability of drugs that target ERα-positive breast cancer, resistance commonly occurs, resulting in relapse, metastasis, and death. Tamoxifen remains the most commonly-prescribed endocrine therapy worldwide, and "tamoxifen resistance" has been extensively studied. However, little consideration has been given to the role of endoxifen, the most abundant active tamoxifen metabolite detected in patients, in driving resistance mechanisms. Read More

BMC Cancer 2021 Feb 22;21(1):185. Epub 2021 Feb 22.

Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.

Background: The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. Read More

J Mol Med (Berl) 2021 Feb 21. Epub 2021 Feb 21.

Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Tamoxifen resistance remains the major obstacle to the estrogen receptor positive breast cancer endocrine therapy. Placenta-specific 8 (PLAC8) has been implicated in epithelial-mesenchymal transition and tumorigenesis. However, the molecular mechanisms underlying PLAC8 function in the context of tamoxifen resistance are unclear. Read More

Biochem Pharmacol 2021 Apr 16;186:114474. Epub 2021 Feb 16.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India. Electronic address:

Conventionally, Cancer-associated fibroblasts (CAFs) are considered as an inducer of chemoresistance in cancer cells. However, the underlying mechanism by which carcinomas induce chemoresistance in CAFs through tumor-stroma cross-talk is largely unknown. Henceforth, we uncovered a network of paracrine signals between carcinoma and CAFs that drives chemoresistance in CAFs. Read More

Int J Cancer 2021 Jun 21;148(11):2848-2856. Epub 2021 Feb 21.

School of Medicine, Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam.

Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anticancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles in 27 data sets on 7244 patients from 11 countries. Read More