scholarly journals Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 929
Author(s):  
Dima Hattab ◽  
Athirah Bakhtiar
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Efficiency ◽  
Growth Factor Receptor ◽  
Chemotherapeutic Agents ◽  
Molecular Signaling ◽  
Breast Cells ◽  
Hormonal Therapies ◽  
Preclinical And Clinical Studies

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective in TNBC patients, making traditional chemotherapeutic agents the only current appropriate regimen. Patients’ predisposition to relapse and metastasis, chemotherapeutics’ cytotoxicity and resistance and poor prognosis of TNBC necessitates researchers to investigate different novel-targeted therapeutics. The role of small interfering RNA (siRNA) in silencing the genes/proteins that are aberrantly overexpressed in carcinoma cells showed great potential as part of TNBC therapeutic regimen. However, targeting specificity, siRNA stability, and delivery efficiency cause challenges in the progression of this application clinically. Nanotechnology was highlighted as a promising approach for encapsulating and transporting siRNA with high efficiency-low toxicity profile. Advances in preclinical and clinical studies utilizing engineered siRNA-loaded nanotherapeutics for treatment of TNBC were discussed. Specific and selective targeting of diverse signaling molecules/pathways at the level of tumor proliferation and cell cycle, tumor invasion and metastasis, angiogenesis and tumor microenvironment, and chemotherapeutics’ resistance demonstrated greater activity via integration of siRNA-complexed nanoparticles.

scholarly journals Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sabrina Bimonte ◽  
Marco Cascella ◽  
Antonio Barbieri ◽  
Claudio Arra ◽  
Arturo Cuomo
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Option ◽  
Growth Factor Receptor ◽  
Natural Substances ◽  
Current State ◽  
Protein Receptors ◽  
Epidermal Growth ◽  
Hormonal Therapies

AbstractTriple-Negative Breast Cancer (TNBC), represents a subtype of breast cancer in which the estrogens receptor (ER) negative, the progesterone receptor (PR) negative and the human epidermal growth factor receptor 2 (HER2) negative, are not expressed. Thusly, TNBC does not respond to hormonal therapies or to those targeting the HER2 protein receptors. To overcome this flawed issue, new alternative therapies based on the use of natural substances, as the (−) - epigallocatechin 3-gallate (EGCG), has been proposed. It is largely documented that EGCG, the principal constituent of green tea, has suppressive effects on different types of cancer, including breast cancer, through the regulation of different signaling pathways. Thus, is reasonable to assume that EGCG could be viewed as a therapeutic option for the prevention and the treatment of TNBC. Here, we summarizing these promising results with the scope of turn a light on the potential roles of EGCG in the treatment of TNBC patients.

Recent advances of nanotechnology in the diagnosis and therapy of triple-negative breast cancer (TNBC)

2021 ◽  
Vol 23 ◽  
Author(s):  
Abhishek Kanugo ◽  
Rupesh K. Gautam ◽  
Mohammad Amjad Kamal
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Efficiency ◽  
Metastatic Cancer ◽  
Chemotherapeutic Agents ◽  
Circulation Time ◽  
Drug Conjugates ◽  
Peptide Drug Conjugates ◽  
Carbon Based

Background: The development of advanced treatment of triple-negative breast cancer (TNBC) is the utmost need of an era. TNBC is recognized as the most aggressive, metastatic cancer and the leading cause of mortality in females worldwide. The lack of expression of triple receptors namely, estrogen, progesterone, and human epidermal receptor2 defined TNBC. Objective: The current review introduced the novel biomarkers such as miRNA and family, PD1, EGFR, VEGF, TILs, P53, AR and PI3K, etc. contributed significantly to the prognosis and diagnosis of TNBC. Once diagnosed the utilization advanced approaches available for TNBC because of the limitations of chemotherapy. Novel approaches include lipid-based (liposomes, SLN, NLC, and SNEDDS), polymer-based (micelle, nanoparticles, dendrimers, and quantum dots), advanced nanocarriers such as (exosomes, antibody and peptide-drug conjugates), carbon-based nanocarriers (Carbon nanotubes, and graphene oxide). Lipid-based delivery is used for excellent carriers for hydrophobic drugs, biocompatibility, and lesser systemic toxicities than chemotherapeutic agents. Polymer-based approaches are preferred over lipids for providing longer circulation time, nanosize, high loading efficiency, high linking; avoiding the expulsion of drugs, targeted action, diagnostic and biosensing abilities. Advanced approaches like exosomes, conjugated moieties are preferred over polymeric for possessing potency, high penetrability, biomarkers, and avoiding the toxicity of tissues. Carbon-based gained wide applicability for their unique properties like a versatile carrier, prognostic, diagnostic, sensing, photodynamic, and photothermal characteristics. Conclusion: The survival rate can be increased by utilizing several kinds of biomarkers. The advanced approaches can also be significantly useful in the prognosis and theranostic of triple-negative breast cancer. One of the biggest successes in treating with nanotechnology-based approaches is the marked reduction of systemic toxicity with high therapeutic effectiveness compared with chemotherapy, surgery, etc. The requirements such as prompt diagnosis, longer circulation time, high efficiency, and high potency, can be fulfilled with these nanocarriers.

scholarly journals Pathogenesis and Potential Therapeutic Targets for Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2978
Author(s):  
Chia-Jung Li ◽  
Yen-Dun Tony Tzeng ◽  
Yi-Han Chiu ◽  
Hung-Yu Lin ◽  
Ming-Feng Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Efficiency ◽  
Early Recurrence ◽  
New Developments ◽  
Great Progress ◽  
Low Toxicity ◽  
Made In

Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.

scholarly journals Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancers ◽  
Targeted Agents ◽  
Increased Risk ◽  
Disproportionate Number

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

scholarly journals Treatment of Triple-Negative Breast Cancer Cells with the Canady Cold Plasma Conversion System: Preliminary Results

Plasma ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 218-228 ◽  
Author(s):  
Xiaoqian Cheng ◽  
Warren Rowe ◽  
Lawan Ly ◽  
Alexey Shashurin ◽  
Taisen Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cold Plasma ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Premenopausal Women ◽  
Atmospheric Plasma ◽  
Starting Point ◽  
Conversion Unit ◽  
Epidermal Growth

Triple-negative breast cancer is a phenotype of breast cancer where the expression level of estrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors are low or absent. It is more frequently diagnosed in younger and premenopausal women, among which African and Hispanic have a higher rate. Cold atmospheric plasma has revealed its promising ant-cancer capacity over the past two decades. In this study, we report the first cold plasma jet delivered by the Canady Cold Plasma Conversion Unit and characterization of its electric and thermal parameters. The unit effectively reduced the viability of triple-negative breast cancer up to 80% without thermal damage, providing a starting point for future clinical trials.

scholarly journals Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5009
Author(s):  
Swetha Vasudevan ◽  
Ibukun A. Adejumobi ◽  
Heba Alkhatib ◽  
Sangita Roy Chowdhury ◽  
Shira Stefansky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Network Structures ◽  
Breast Cancers ◽  
Drug Induced ◽  
Tcga Dataset

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1–4 altered protein–protein subnetworks. Thirty-one percent of TNBC PaSSSs were found to harbor EGFR as a part of the network and were predicted to benefit from anti-EGFR therapy as long as it is combined with anti-estrogen receptor (ER) therapy. Using a series of single-cell experiments, followed by in vivo support, we show that drug combinations which are not tailored accurately to each PaSSS may generate evolutionary pressure in malignancies leading to an expansion of the previously undetected or untargeted subpopulations, such as ER+ populations. This corresponds to the PaSSS-based predictions suggesting to incorporate anti-ER drugs in certain anti-TNBC treatments. These findings highlight the need to tailor anti-TNBC targeted therapy to each PaSSS to prevent diverse evolutions of TNBC tumors and drug resistance development.

scholarly journals Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Hippo Signaling ◽  
Luminal A ◽  
Luminal B ◽  
Epidermal Growth

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

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