scholarly journals Role of estrogen receptor coregulators in endocrine resistant breast cancer

2021 ◽  
pp. 385-400
Author(s):  
Kristin A. Altwegg ◽  
Ratna K. Vadlamudi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Therapy Resistance ◽  
Vital Role ◽  
In Vivo Studies ◽  
Scaffolding Proteins ◽  
Current State ◽  
Er Alpha

Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70-80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC.

scholarly journals Selective Targeting of Breast Cancer by Tafuramycin a Using SMA-Nanoassemblies

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3532
Author(s):  
Ibrahim M. El-Deeb ◽  
Valeria Pittala ◽  
Diab Eltayeb ◽  
Khaled Greish
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptors ◽  
In Vivo Studies ◽  
Chemotherapy Agent ◽  
Anticancer Effects ◽  
Tumor Tissues ◽  
Potential Strategy ◽  
Tumor Accumulation

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumors that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. The mainstay of treatment remains chemotherapy, but the therapeutic outcome remains inadequate. This paper investigates the potential of a duocarmycin derivative, tafuramycin A (TFA), as a new and more effective chemotherapy agent in TNBC treatment. To this extent, we optimized the chemical synthesis of TFA, and we encapsulated TFA in a micellar system to reduce side effects and increase tumor accumulation. In vitro and in vivo studies suggest that both TFA and SMA–TFA possess high anticancer effects in TNBC models. Finally, the encapsulation of TFA offered a preferential avenue to tumor accumulation by increasing its concentration at the tumor tissues by around four times in comparison with the free drug. Overall, the results provide a new potential strategy useful for TNBC treatment.

scholarly journals CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 898
Author(s):  
Ghazal Nabil ◽  
Rami Alzhrani ◽  
Hashem Alsaab ◽  
Mohammed Atef ◽  
Samaresh Sau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
In Vivo Studies ◽  
High Dose ◽  
Luminal A ◽  
Combination Strategy ◽  
Ongoing Research

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

Analysis on Homoeopathic Preparation of Asterias Rubens for Evaluating Anti Breast Cancer Cell Line using Similia Principle

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
In Vitro Study ◽  
In Vivo Studies ◽  
Asterias Rubens ◽  
Mcf 7

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.

scholarly journals Blockade of CDK7 Reverses Endocrine Therapy Resistance in Breast Cancer

2020 ◽  
Vol 21 (8) ◽  
pp. 2974 ◽  
Author(s):  
Yasmin M. Attia ◽  
Samia A. Shouman ◽  
Salama A. Salama ◽  
Cristina Ivan ◽  
Abdelrahman M. Elsayed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Volume ◽  
Apoptotic Cell ◽  
Therapy Resistance ◽  
Tamoxifen Treatment ◽  
Clinical Samples ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients

Cyclin-dependent kinase (CDK)-7 inhibitors are emerging as promising drugs for the treatment of different types of cancer that show chemotherapy resistance. Evaluation of the effects of CDK7 inhibitor, THZ1, alone and combined with tamoxifen is of paramount importance. Thus, in the current work, we assessed the effects of THZ1 and/or tamoxifen in two estrogen receptor-positive (ER+) breast cancer cell lines (MCF7) and its tamoxifen resistant counterpart (LCC2) in vitro and in xenograft mouse models of breast cancer. Furthermore, we evaluated the expression of CDK7 in clinical samples from breast cancer patients. Cell viability, apoptosis, and genes involved in cell cycle regulation and tamoxifen resistance were determined. Tumor volume and weight, proliferation marker (Ki67), angiogenic marker (CD31), and apoptotic markers were assayed. Bioinformatic data indicated CDK7 expression was associated with negative prognosis, enhanced pro-oncogenic pathways, and decreased response to tamoxifen. Treatment with THZ1 enhanced tamoxifen-induced cytotoxicity, while it inhibited genes involved in tumor progression in MCF-7 and LCC2 cells. In vivo, THZ1 boosted the effect of tamoxifen on tumor weight and tumor volume, reduced Ki67 and CD31 expression, and increased apoptotic cell death. Our findings identify CDK7 as a possible therapeutic target for breast cancer whether it is sensitive or resistant to tamoxifen therapy.

In vitro and in vivo studies of gold(I) azolate/phosphane complexes for the treatment of basal like breast cancer

2018 ◽  
Vol 155 ◽  
pp. 418-427 ◽  
Author(s):  
Valentina Gambini ◽  
Martina Tilio ◽  
Eunice Wairimu Maina ◽  
Cristina Andreani ◽  
Caterina Bartolacci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Vivo Studies ◽  
Basal Like Breast Cancer

scholarly journals Breast Cancer Prevention-Is there a Future for Sulforaphane and Its Analogs?

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1559
Author(s):  
Dominika Kuran ◽  
Anna Pogorzelska ◽  
Katarzyna Wiktorska
Keyword(s):  
Breast Cancer ◽  
Cancer Prevention ◽  
Initial Study ◽  
Dietary Factors ◽  
Breast Cancer Prevention ◽  
In Vivo Studies ◽  
Cancer Etiology ◽  
The Impact

Breast cancer is the most prevalent type of cancer among women worldwide. There are several recommended methods of breast cancer prevention, including chemoprevention. There are several approved drugs used to prevent breast cancer occurrence or recurrence and metastasizing. There are also a number of new substances undergoing clinical trials and at the stage of initial study. Studies suggest that dietary factors play a crucial role in breast cancer etiology. Epidemiological studies indicate that in particular vegetables from the Brassicaceae family are a rich source of chemopreventive substances, with sulforaphane (SFN) being one of the most widely studied and characterized. This review discusses potential applicability of SFN in breast cancer chemoprevention. A comprehensive review of the literature on the impact of SFN on molecular signalling pathways in breast cancer and breast untransformed cells is presented. The presented results of in vitro and in vivo studies show that this molecule has a potential to act as a preventive molecule either to prevent disease development or recurrence and metastasizing, and as a compound protecting normal cells against the toxic effects of cytostatics. Finally, the still scanty attempts to develop an improved analog are also presented and discussed.

Recombinant Human Erythropoietin (rHuEPO) In Combination with Chemotherapy Increases Breast Cancer Metastasis In Pre-Clinical Mouse Models

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3345-3345
Author(s):  
Anargyros Xenocostas ◽  
Benjamin D Hedley ◽  
Jenny E Chu ◽  
D. George Ormond ◽  
Michel Beausoleil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Research Funding ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
In Vivo Studies ◽  
Metastatic Process

Abstract Abstract 3345 Background: Erythropoietin (EPO) is a key regulator of erythropoiesis, and has been shown to stimulate growth, maintain viability, and promote differentiation of red blood cell precursors. The EPO receptor (EPO-R) is expressed by erythroid cells and by several non-hematopoietic cell types including various neoplastic cells. Erythropoiesis-stimulating agents (ESAs) are used clinically for the treatment of chemotherapy-induced anemia. The results of some recent randomized clinical trials have reported an increased incidence in adverse events and reduced survival in ESA-treated metastatic breast cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression. These results have raised concerns over ESA treatment in metastatic cancer patients. However, very little pre-clinical data is available regarding the impact of EPO on breast cancer metastasis. The goal of the current study was therefore to determine if EPO can influence the malignant behavior of breast cancer cells and/or influence the metastatic process. Methods: MDA-MB-468, MDA-MB-231, MDA-MB-435, and 4T-1 breast cancer cell lines were treated with recombinant human EPO (rHuEPO; 10 U/ml) or control media and screened for EPO-R mRNA expression levels by RT-PCR, and for EPO-R protein expression by Western blot and flow cytometry. MDA-MB-231 (231) and MDA-MB-435 (435) cell lines were used for functional assays in vitro and in vivo. Untreated or rHuEPO treated cells were grown in 2D and 3D in vitro systems (standard tissue culture plates and 0.6% soft agar, respectively) to determine if rHuEPO influenced growth. In vitro cell survival was also assessed in response to treatment with rHuEPO in the presence or absence of paclitaxel chemotherapy (10mg/ml), radiation (10G), or hypoxic conditions (1% O2). Following mammary fat pad injection, in vivo effects of rHuEPO (300U/kg) alone or in combination with paclitaxel treatment (10mg/kg) were assessed in mouse models of tumorigenicity and spontaneous metastasis. Results: Expression analysis of EPO-R mRNA and protein revealed a large variation in levels across different cell lines. The majority of cell lines did not express cell surface EPO-R by flow cytometry, although two cell lines (231 and 435) did show weak expression of EPO-R mRNA, with only the 231 cell line showing EPO-R expression by Western blot. In vitro, a small protective effect from rHuEPO on radiation-treated 435 cells was seen (p<0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not cause a significant increase in cell survival relative to untreated controls cells. In contrast, in vivo studies demonstrated that rHuEPO increased the incidence and burden of lung metastases in immunocompromised mice injected with 231 or 435 cells and treated with paclitaxel relative to mice treated with paclitaxel alone (p<0.05). Conclusions: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. Our novel findings demonstrate that rHuEPO can reduce the efficacy of chemotherapy in the metastatic setting in vivo, and in some cases enhance the inherent metastatic growth potential of human breast cancer cells. This work was supported by funding from the London Regional Cancer Program and Janssen Ortho Canada Disclosures: Xenocostas: Janssen Ortho: Consultancy, Honoraria, Research Funding. Allan:Janssen Ortho: Research Funding.

Therapeutic monoclonal antibodies target phenotypically-differing human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Human Breast ◽  
Breast Cancer Model ◽  
Cancer Tissues

13510 Background: CD44 (an adhesion molecule and stem cell antigen), CD59 (a complement-inhibitory molecule), MCSP (an adhesion and cell-cell interactions), and Trop-2 (EpCam a related signaling molecule) represent a group of biologically-significant cancer proteins acting through distinct mechanisms. We have described Abs with in vitro and in vivo cancer suppressive activity to this group of targets. However, their effectiveness depends on the phenotype of malignant cells; cell response should correlate with expression of its Ag, and tumor cells represent a heterogeneous group of non-synchronous cells. The present study describes the efficacy of those antibodies in breast cancer models and the prevalence of their antigen targets in a survey of human breast cancer tissues. Methods: In vivo activity of antibodies ARH460–16–2 (anti-CD44), AR36A36.11.1 (anti-CD59), AR11BD-2E11–2 (anti-MCSP), and AR47A6.4.2 (anti-Trop-2) in estrogen-dependent and hormone sensitive xenograft models of human breast cancer was examined. In addition, distribution of the antigens in breast cancer was determined by immunohistochemistry using tumor tissue arrays of breast cancer sections from distinct patients. Results: Treatment of an established breast cancer model with ARH460–16–2 resulted in 51% median tumor xenograft suppression (p<0.05), as well as increased survival in an MDA-MB-231 (breast cancer) grafted model. 63% of human breast cancer sections expressed the CD44 antigen. Treatment with anti-CD59 antibody AR36A36.11.1 resulted in 68% xenograft tumor suppression (p<0.005). AR47A6.4.2 anti-Trop-2 antibody bound to 100% of human breast cancer sections tested, and showed efficacy in the estrogen- dependent MCF-7 breast cancer model. Anti-MCSP antibody AR11BD-2E11–2 demonstrated 80% tumor growth inhibition (p<0.001), increased survival in an estrogen-dependent model of breast cancer, and was found to stain 62% of breast cancer tissues examined. Conclusions: The heterogeneity of breast cancer cell phenotypes in in vitro and in vivo studies and variable composite cellular antigen targets is the basis for the therapeutic use of multiple antibodies, each with independent mechanisms of action, and offers a rationale for combined antibody therapy in selected patients. [Table: see text]

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