International Journal of Molecular Sciences

Editorial

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Open AccessEditorial

Editorial for the Special Issue “New Drugs for Breast Cancer Treatment”

by Filippo Acconcia

Int. J. Mol. Sci. 2022, 23(18), 10265; https://doi.org/10.3390/ijms231810265 - 6 Sep 2022

Viewed by 1129

Abstract

Breast cancer (BC) is the deadliest neoplastic disease for women worldwide [...] Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

Research

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9 pages, 1195 KiB

Open AccessArticle

LC–MS Based Lipidomics Depict Phosphatidylethanolamine as Biomarkers of TNBC MDA-MB-231 over nTNBC MCF-7 Cells

by Alan Rubén Estrada-Pérez, Norbert Bakalara, Juan Benjamín García-Vázquez, Martha Cecilia Rosales-Hernández, Cynthia Fernández-Pomares and José Correa-Basurto

Int. J. Mol. Sci. 2022, 23(20), 12074; https://doi.org/10.3390/ijms232012074 - 11 Oct 2022

Cited by 5 | Viewed by 1843

Abstract

Breast cancer (BC) is the first malignant neoplasm in women, with a high death rate despite early diagnoses and treatment advances. Significant differences exist between the most common BC and triple-negative breast cancer (TNBC). TNBC presents molecular differences such as lacking expression of [...] Read more.

Breast cancer (BC) is the first malignant neoplasm in women, with a high death rate despite early diagnoses and treatment advances. Significant differences exist between the most common BC and triple-negative breast cancer (TNBC). TNBC presents molecular differences such as lacking expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2 proteins, making this cancer have a poor clinical prognostic and lack clear strategies for its treatment. However, growing evidence points to metabolic dysregulation as another differential process between stages and types of BC. Therefore, the study of this crucial hallmark could identify new therapeutic targets to treat this aggressive form of BC. These differences induce an in vitro exploration of the metabolic behavior of the MCF7 cells (nTNBC) and MDA-MB-231 (TNBC) cells under lipidomic based LC–MS. The results show more significant differences in lipid regulation (phosphatidylethanolamine) that could be associated with the aggressiveness and difficulties of the treatment of TNBC. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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14 pages, 4463 KiB

Open AccessArticle

AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

by Marine Geoffroy, Marine Lemesle, Alexandra Kleinclauss, Sabine Mazerbourg, Levy Batista, Muriel Barberi-Heyob, Thierry Bastogne, Wilfrid Boireau, Alain Rouleau, Dorian Dupommier, Michel Boisbrun, Corinne Comoy, Stéphane Flament, Isabelle Grillier-Vuissoz and Sandra Kuntz

Int. J. Mol. Sci. 2022, 23(12), 6859; https://doi.org/10.3390/ijms23126859 - 20 Jun 2022

Cited by 4 | Viewed by 2535

Abstract

Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two [...] Read more.

Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ and AB186. Previous studies showed that both compounds induce apoptosis, nevertheless AB186 was a more potent agent. The kinetic of cellular events was investigated by real-time cell analysis system (RTCA) in MCF-7 (hormone dependent) and MDA-MB-231 (triple negative) breast cancer (TNBC) cells, followed by cell morphology analysis by immuno-localization. Both compounds induced a rapid modification of both impedance-based signals and cellular morphology. This process was associated with an inhibition of cell migration measured by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cells. In order to identify cytoplasmic targets of AB186, we performed surface plasmon resonance (SPR) and pull-down analyses. Subsequently, 6 cytoskeleton components were identified as potential targets. We further validated α-tubulin as one of the direct targets of AB186. In conclusion, our results suggested that AB186 could be promising to develop novel therapeutic strategies to treat aggressive forms of breast cancer such as TNBC. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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9 pages, 1227 KiB

Open AccessArticle

Untargeted LC-MS/MS Metabolomics Study on the MCF-7 Cell Line in the Presence of Valproic Acid

by Alan Rubén Estrada-Pérez, Martha Cecilia Rosales-Hernández, Juan Benjamín García-Vázquez, Norbert Bakalara, Benedicte Fromager and José Correa-Basurto

Int. J. Mol. Sci. 2022, 23(5), 2645; https://doi.org/10.3390/ijms23052645 - 28 Feb 2022

Cited by 8 | Viewed by 2688

Abstract

To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to [...] Read more.

To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to be studied in depth to understand the effects it might elicit in BC cells. The aim of this work is to contribute to exploring the complete pharmacological mechanism of VPA in killing cancer cells using MCF-7. LC-MS/MS metabolomics studies were applied to MCF-7 treated with VPA. The results show that VPA promote cell death by altering metabolic pathways principally pentose phosphate pathway (PPP) and 2′deoxy-α-D-ribose-1-phosphate degradation related with metabolites that decrease cell proliferation and cell growth, interfere with energy sources and enhance reactive oxygen species (ROS) levels. We even suggest that mechanisms such as ferropoptosis could be involved due to deregulation of L-cysteine. These results suggest that VPA has different pharmacological mechanisms in killing cancer cells including apoptotic and nonapoptotic mechanisms, and due to the broad impact that HDACis have in cells, metabolomic approaches are a great source of information to generate new insights for this type of molecule. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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11 pages, 2571 KiB

Open AccessArticle

Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level

by Agne Janoniene, Linas Mazutis, Daumantas Matulis and Vilma Petrikaite

Int. J. Mol. Sci. 2021, 22(21), 11571; https://doi.org/10.3390/ijms222111571 - 26 Oct 2021

Cited by 6 | Viewed by 2494

Abstract

Protein Carbonic Anhydrase IX (CA IX), which is expressed in various hypoxic solid tumors in order to maintain proper pH, is also related to cancer cell adhesion, invasion, and metastasis processes. Here, we investigated whether CA IX inhibition by a highly CA IX [...] Read more.

Protein Carbonic Anhydrase IX (CA IX), which is expressed in various hypoxic solid tumors in order to maintain proper pH, is also related to cancer cell adhesion, invasion, and metastasis processes. Here, we investigated whether CA IX inhibition by a highly CA IX selective agent benzenesulfonamide VD11-4-2 triggers changes in individual cell motility. We seeded breast cancer cells on an extracellular matrix-coated glass-bottomed dish and in a microfluidic device with a gradient flow of epidermal growth factor (EGF), tracked individual cell movement, calculated their migration speeds, and/or followed movement direction. Our results showed that the inhibitor VD11-4-2 decreased the speed of CA IX positive breast cancer cells by 20–26% while not affecting non-cancerous cell migration. The inhibitor suppressed the cell migration velocity increment and hindered cells from reaching their maximum speed. VD11-4-2 also reduced CA IX, expressing cell movement towards the growth factor as a chemoattractant. Such a single cell-based migration assay enabled the comprehensive investigation of the cell motility and revealed that VD11-4-2 shows the ability to suppress breast cancer cell migration at a lower concentration than previously tested CA IX inhibitors. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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18 pages, 34130 KiB

Open AccessArticle

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

by Kitti Andreidesz, Aliz Szabo, Dominika Kovacs, Balazs Koszegi, Viola Bagone Vantus, Eszter Vamos, Mostafa Isbera, Tamas Kalai, Zita Bognar, Krisztina Kovacs and Ferenc Gallyas

Int. J. Mol. Sci. 2021, 22(16), 9016; https://doi.org/10.3390/ijms22169016 - 20 Aug 2021

Cited by 6 | Viewed by 2486

Abstract

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and [...] Read more.

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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13 pages, 3149 KiB

Open AccessArticle

Optical Redox Imaging of Treatment Responses to Nampt Inhibition and Combination Therapy in Triple-Negative Breast Cancer Cells

by Allison Podsednik, Jinxia Jiang, Annemarie Jacob, Lin Z. Li and He N. Xu

Int. J. Mol. Sci. 2021, 22(11), 5563; https://doi.org/10.3390/ijms22115563 - 25 May 2021

Cited by 10 | Viewed by 2989

Abstract

We evaluated the utility of optical redox imaging (ORI) to identify the therapeutic response of triple-negative breast cancers (TNBC) under various drug treatments. Cultured HCC1806 and MDA-MB-231 cells treated with FK866 (nicotinamide phosphoribosyltransferase (Nampt) inhibitor), FX11 (lactate dehydrogenase A inhibitor), paclitaxel, and their [...] Read more.

We evaluated the utility of optical redox imaging (ORI) to identify the therapeutic response of triple-negative breast cancers (TNBC) under various drug treatments. Cultured HCC1806 and MDA-MB-231 cells treated with FK866 (nicotinamide phosphoribosyltransferase (Nampt) inhibitor), FX11 (lactate dehydrogenase A inhibitor), paclitaxel, and their combinations were subjected to ORI, followed by imaging fluorescently labeled reactive oxygen species (ROS). Cell growth inhibition was measured by a cell viability assay. We found that both cell lines experienced significant NADH decrease and redox ratio (Fp/(NADH+Fp)) increase due to FK866 treatment; however, HCC1806 was much more responsive than MDA-MB-231. We further studied HCC1806 with the main findings: (i) nicotinamide riboside (NR) partially restored NADH in FK866-treated cells; (ii) FX11 induced an over 3-fold NADH increase in FK866 or FK866+NR pretreated cells; (iii) FK866 combined with paclitaxel caused synergistic increases in both Fp and the redox ratio; (iv) FK866 sensitized cells to paclitaxel treatments, which agrees with the redox changes detected by ORI; (v) Fp and the redox ratio positively correlated with cell growth inhibition; and (vi) Fp and NADH positively correlated with ROS level. Our study supports the utility of ORI for detecting the treatment responses of TNBC to Nampt inhibition and the sensitization effects on standard chemotherapeutics. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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16 pages, 2147 KiB

Open AccessArticle

Atovaquone Suppresses Triple-Negative Breast Tumor Growth by Reducing Immune-Suppressive Cells

by Nehal Gupta, Shreyas Gaikwad, Itishree Kaushik, Stephen E. Wright, Maciej M. Markiewski and Sanjay K. Srivastava

Int. J. Mol. Sci. 2021, 22(10), 5150; https://doi.org/10.3390/ijms22105150 - 13 May 2021

Cited by 23 | Viewed by 3621

Abstract

A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and [...] Read more.

A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and induce regulatory T cells (Tregs), all of which are immunosuppressive and enhance tumor progression. Hence, enhancing the immune system in breast tumors could be a strategy for anticancer therapeutics. The present study evaluated the immune response of atovaquone, an antiprotozoal drug, in three independent breast-tumor models. Our results demonstrated that oral administration of atovaquone reduced HCC1806, CI66 and 4T1 paclitaxel-resistant (4T1-PR) breast-tumor growth by 45%, 70% and 42%, respectively. MDSCs, TGF-β, IL-10 and Tregs of blood and tumors were analyzed from all of these in vivo models. Our results demonstrated that atovaquone treatment in mice bearing HCC1806 tumors reduced MDSCs from tumor and blood by 70% and 30%, respectively. We also observed a 25% reduction in tumor MDSCs in atovaquone-treated mice bearing CI66 and 4T1-PR tumors. In addition, a decrease in TGF-β and IL-10 in tumor lysates was observed in atovaquone-treated mice with a reduction in tumor Tregs. Moreover, a significant reduction in the expression of RPS19 was found in tumors treated with atovaquone. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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28 pages, 5711 KiB

Open AccessArticle

Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation

by Kutlwano R. Xulu and Tanya N. Augustine

Int. J. Mol. Sci. 2021, 22(8), 4153; https://doi.org/10.3390/ijms22084153 - 16 Apr 2021

Cited by 8 | Viewed by 3456

Abstract

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole [...] Read more.

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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18 pages, 4063 KiB

Open AccessArticle

A New Anti-Estrogen Discovery Platform Identifies FDA-Approved Imidazole Anti-Fungal Drugs as Bioactive Compounds against ERα Expressing Breast Cancer Cells

by Manuela Cipolletti, Stefania Bartoloni, Claudia Busonero, Martina Parente, Stefano Leone and Filippo Acconcia

Int. J. Mol. Sci. 2021, 22(6), 2915; https://doi.org/10.3390/ijms22062915 - 13 Mar 2021

Cited by 12 | Viewed by 3074

Abstract

17β-estradiol (E2) exerts its physiological effects through the estrogen receptor α (i.e., ERα). The E2:ERα signaling allows the regulation of cell proliferation. Indeed, E2 sustains the progression of ERα positive (ERα+) breast cancers (BCs). The presence of ERα at the BC diagnosis drives [...] Read more.

17β-estradiol (E2) exerts its physiological effects through the estrogen receptor α (i.e., ERα). The E2:ERα signaling allows the regulation of cell proliferation. Indeed, E2 sustains the progression of ERα positive (ERα+) breast cancers (BCs). The presence of ERα at the BC diagnosis drives their therapeutic treatment with the endocrine therapy (ET), which restrains BC progression. Nonetheless, many patients develop metastatic BCs (MBC) for which a treatment is not available. Consequently, the actual challenge is to complement the drugs available to fight ERα+ primary and MBC. Here we exploited a novel anti-estrogen discovery platform to identify new Food and Drug Administration (FDA)-approved drugs inhibiting E2:ERα signaling to cell proliferation in cellular models of primary and MBC cells. We report that the anti-fungal drugs clotrimazole (Clo) and fenticonazole (Fenti) induce ERα degradation and prevent ERα transcriptional signaling and proliferation in cells modeling primary and metastatic BC. The anti-proliferative effects of Clo and Fenti occur also in 3D cancer models (i.e., tumor spheroids) and in a synergic manner with the CDK4/CDK6 inhibitors palbociclib and abemaciclib. Therefore, Clo and Fenti behave as “anti-estrogens”-like drugs. Remarkably, the present “anti-estrogen” discovery platform represents a valuable method to rapidly identify bioactive compounds with anti-estrogenic activity. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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17 pages, 14564 KiB

Open AccessArticle

Newly Synthesized Imino-Derivatives Analogues of Resveratrol Exert Inhibitory Effects in Breast Tumor Cells

by Domenico Iacopetta, Rosamaria Lappano, Annaluisa Mariconda, Jessica Ceramella, Maria Stefania Sinicropi, Carmela Saturnino, Marianna Talia, Francesca Cirillo, Fabio Martinelli, Francesco Puoci, Camillo Rosano, Pasquale Longo and Marcello Maggiolini

Int. J. Mol. Sci. 2020, 21(20), 7797; https://doi.org/10.3390/ijms21207797 - 21 Oct 2020

Cited by 29 | Viewed by 3082

Abstract

Breast cancer represents the most frequently diagnosed malignancy in women worldwide. Various therapeutics are currently used in order to halt the progression of breast tumor, even though certain side effects may limit the beneficial effects. In recent years, many efforts have been addressed [...] Read more.

Breast cancer represents the most frequently diagnosed malignancy in women worldwide. Various therapeutics are currently used in order to halt the progression of breast tumor, even though certain side effects may limit the beneficial effects. In recent years, many efforts have been addressed to the usefulness of natural compounds as anticancer agents due to their low toxicity. Resveratrol, a stilbene found in grapes, berries, peanuts and soybeans, has raised a notable interest for its antioxidant, anti-inflammatory, and antitumor properties. Here, we report the design, the synthesis and the characterization of the anticancer activity of a small series of imino N-aryl-substituted compounds that are analogues of resveratrol. In particular, the most active compound, named 3, exhibited anti-tumor activity in diverse types of breast cancer cells through the inhibition of the human topoisomerase II and the induction of apoptotic cell death. Therefore, the abovementioned compound maybe considered as a promising agent in more comprehensive treatments of breast cancer. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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Review

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20 pages, 1516 KiB

Open AccessReview

New and Emerging Targeted Therapies for Advanced Breast Cancer

by Kristie H. Lau, Alexandra M. Tan and Yihui Shi

Int. J. Mol. Sci. 2022, 23(4), 2288; https://doi.org/10.3390/ijms23042288 - 18 Feb 2022

Cited by 80 | Viewed by 8717

Abstract

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression [...] Read more.

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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18 pages, 412 KiB

Open AccessReview

Breast Cancer and Anaesthesia: Genetic Influence

by Aida Raigon Ponferrada, Jose Luis Guerrero Orriach, Juan Carlos Molina Ruiz, Salvador Romero Molina, Aurelio Gómez Luque and Jose Cruz Mañas

Int. J. Mol. Sci. 2021, 22(14), 7653; https://doi.org/10.3390/ijms22147653 - 17 Jul 2021

Cited by 10 | Viewed by 3706

Abstract

Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical [...] Read more.

Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical and morphological heterogeneity of the different types of breast tumors has led to a diversity of staging and classification systems. Thus, these tumors show wide variability in genetic expression and prognostic biomarkers. Surgical treatment is essential in the management of these patients. However, the perioperative period has been found to significantly influence survival and cancer recurrence. There is growing interest in the pro-tumoral effect of different anaesthetic and analgesic agents used intraoperatively and their relationship with metastatic progression. There is cumulative evidence of the influence of anaesthetic techniques on the physiopathological mechanisms of survival and growth of the residual neoplastic cells released during surgery. Prospective randomized clinical trials are needed to obtain quality evidence on the relationship between cancer and anaesthesia. This document summarizes the evidence currently available about the effects of the anaesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

17 pages, 1904 KiB

Open AccessReview

Theranostic Advances in Breast Cancer in Nuclear Medicine

by Nasim Vahidfar, Ayuob Aghanejad, Hojjat Ahmadzadehfar, Saeed Farzanehfar and Elisabeth Eppard

Int. J. Mol. Sci. 2021, 22(9), 4597; https://doi.org/10.3390/ijms22094597 - 27 Apr 2021

Cited by 50 | Viewed by 7848

Abstract

The implication of ‘theranostic’ refers to targeting an identical receptor for diagnostic and therapeutic purposes, by the same radioligand, simultaneously or separately. In regard to extensive efforts, many considerable theranostic tracers have been developed in recent years. Emerging evidence strongly demonstrates the tendency [...] Read more.

The implication of ‘theranostic’ refers to targeting an identical receptor for diagnostic and therapeutic purposes, by the same radioligand, simultaneously or separately. In regard to extensive efforts, many considerable theranostic tracers have been developed in recent years. Emerging evidence strongly demonstrates the tendency of nuclear medicine towards therapies based on a diagnosis. This review is focused on the examples of targeted radiopharmaceuticals for the imaging and therapy of breast cancer. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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19 pages, 3178 KiB

Open AccessReview

Glucocorticoid Receptor: A Multifaceted Actor in Breast Cancer

by Lara Malik Noureddine, Olivier Trédan, Nader Hussein, Bassam Badran, Muriel Le Romancer and Coralie Poulard

Int. J. Mol. Sci. 2021, 22(9), 4446; https://doi.org/10.3390/ijms22094446 - 24 Apr 2021

Cited by 29 | Viewed by 5326

Abstract

Breast cancer (BC) is one of the most common cancers in women worldwide. Even though the role of estrogen receptor alpha (ERα) is extensively documented in the development of breast tumors, other members of the nuclear receptor family have emerged as important players. [...] Read more.

Breast cancer (BC) is one of the most common cancers in women worldwide. Even though the role of estrogen receptor alpha (ERα) is extensively documented in the development of breast tumors, other members of the nuclear receptor family have emerged as important players. Synthetic glucocorticoids (GCs) such as dexamethasone (dex) are commonly used in BC for their antiemetic, anti-inflammatory, as well as energy and appetite stimulating properties, and to manage the side effects of chemotherapy. However, dex triggers different effects depending on the BC subtype. The glucocorticoid receptor (GR) is also an important marker in BC, as high GR expression is correlated with a poor and good prognosis in ERα-negative and ERα-positive BCs, respectively. Indeed, though it drives the expression of pro-tumorigenic genes in ERα-negative BCs and is involved in resistance to chemotherapy and metastasis formation, dex inhibits estrogen-mediated cell proliferation in ERα-positive BCs. Recently, a new natural ligand for GR called OCDO was identified. OCDO is a cholesterol metabolite with oncogenic properties, triggering mammary cell proliferation in vitro and in vivo. In this review, we summarize recent data on GR signaling and its involvement in tumoral breast tissue, via its different ligands. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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11 pages, 1252 KiB

Open AccessBrief Report

Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer

by Elisa Pierpaoli, Francesco Piacenza, Gaetano Fiorillo, Paolo Lombardi, Fiorenza Orlando, Carmela Salvatore, Cristina Geroni and Mauro Provinciali

Int. J. Mol. Sci. 2021, 22(5), 2653; https://doi.org/10.3390/ijms22052653 - 6 Mar 2021

Cited by 6 | Viewed by 2514

Abstract

The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of [...] Read more.

The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer. Full article

(This article belongs to the Special Issue New Drugs for Breast Cancer Treatment)

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