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 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 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.

Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion of MDA-MB-231 Triple-Negative Breast Cancer Cell via Induction of Autophagy

2020 ◽  
Vol 19 (16) ◽  
pp. 1983-1990 ◽  
Author(s):  
Hui-Yuan Lu ◽  
Jian-Sheng Zhu ◽  
Zhan Zhang ◽  
Wei-Jian Shen ◽  
Shan Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Viability ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cell Migration And Invasion

Background: Breast Cancer (BC) is the leading cause of cancer-related deaths among women. As such, novel chemotherapeutic agents are urgently needed, especially for Triple-Negative Breast Cancer (TNBC). Hydroxytyrosol (HT) and Oleuropein (OL) are rich in olive oil, which is associated with a low occurrence of BC. However, the effects and mechanisms of action of HT and OL in BC cells are still unclear. This study aimed to explore the molecular mechanisms underlying the antitumor effect of HT and OL in TNBC. Methods: TNBC MDA-MB-231 cells were treated with HT and OL in combination with Hepatocyte Growth Factor (HGF), rapamycin (Rapa, an inducer of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy). Cell viability, migration, invasion, and autophagy signaling were analyzed by scratch assays, transwell migration assays, and Western blot analysis. Results: Treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner. MDAMB- 231 cells were more sensitive to HT treatment than OL treatment. Rapa treatment could significantly block HGF-induced MDA-MB-231 cell migration and invasion, suggesting that inhibition of autophagy could promote migration and invasion. Moreover, HT or OL treatment significantly suppressed HGF or 3-MA induced cell migration and invasion by reversing LC3-II/LC3-I and Beclin-1 downregulation and reversing p62 upregulation. Conclusion: These data indicated that HT and OL may inhibit migration and invasion of TNBC cells by activating autophagy. These findings provide potential therapeutic strategies that target autophagy to limit the pathogenesis and progression of BC.

Prelimenary results of a phase I/II of a combination of cetuximab and taxane for triple negative breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12018-e12018
Author(s):  
H. Nechushtan ◽  
H. Steinberg ◽  
T. Peretz
Keyword(s):  
Breast Cancer ◽  
Tumor Marker ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Patient Characteristics ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Patients ◽  
Egfr Expression ◽  
Nail Disease

e12018 Background: The triple negative subtype of breast cancer is currently only treated with chemotherapeutic agents. It has been demonstrated that over 50% of this kind of tumors express EGFR (HER-1). Cetuximab is a humanized antiEGFR IgG1 antibody. In colon cancer there are also high percentage of EGFR expression and addition of Cetuximab to chemotherapy results in renewed sensitivity to treatments. We therefore hypothesized that in a similar manner addition of Cetuximab to taxanes which are among the most potent anti breast cancer drugs will result in increased effectiveness in this subset of breast cancer patients. Methods: From January 2007 to January 2009, we treated 12 breast cancer patients with either paclitaxel 80 mg/m2, (10 patients) or docetaxel (30 mg mg/m2) (2 patients), with cetuximab weekly. Patients had a pathology sample of breast cancer with triple negative components, metastatic disease and up to two prior chemotherapy lines in the metastatic settings. Results: Patient characteristics (median): age 60 (31–69) years, prior taxane therapy 9/12 pts. Toxicity: Dermatologic grade 2 9/12 grade 3 3/12, nail disease grade 2 10/12 evaluable patients. One patient developed severe swallowing difficulties after 19 month of therapy which may or may not be linked to the treatment. Response is evaluable for 11/12 patients. Response which includes clinical response, tumor marker decrease, and a metastasis size decrease was noted in 9/11 patients. Including tumor marker normalization and nearly a roentgoenolgic CR in a young patient previously treated with several chemeotherapietic lines. Three patients developed brain metastasis during treatments. Molecular pathology is now performed. We continue accrual. Conclusions: Administration of taxane-cetuximab weekly therapy for triple negative breast cancer patients is possible. Toxicity is the cumulated expected toxicity of each of the agents — special care should be taken for nail disease which occurred in most of the patients. Some impressive clinical responses were obtained even in taxane pretreated patients. [Table: see text]

Blocking pro-invasive signaling and inflammatory activation in triple-negative breast cancer with nucleic-acid scavengers (NASs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13096-e13096
Author(s):  
Elias Eteshola ◽  
Karenia Landa ◽  
Eun-Sil Shelley Hwang ◽  
Smita Nair ◽  
Bruce Sullenger
Keyword(s):  
Breast Cancer ◽  
Nucleic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Chemotherapeutic Agents ◽  
Metastatic Progression ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Insight Into

e13096 Background: Breast cancers remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive potential are believed to be the major contributors of these outcomes. Triple-negative breast cancer (TNBC) are notoriously aggressive, difficult-to-treat, and metastatic. Inflammation-driven tumorigenesis has been shown to correlate with cell-free DNA (cfDNA) and other damage-associated molecular patterns (DAMPs) in cancer patient sera. We showed that nucleic-acid scavengers (NAS) can block pro-inflammatory signals elicited by DAMP-activation of innate immune sensors (e.g. toll-like receptors). Treatment with the NAS PAMAM-G3 drastically reduced liver metastatic burden in an immunocompetent murine model of pancreatic cancer. Methods: TNBC cells lines were treated with a cocktail of standard-of-care chemotherapeutic agents and the conditioned media (CM) from these cells served as an in vitro DAMP source. Downstream function of TLR activation was tested via a HEK293-TLR reporter cell line measuring absorbance at 655nm. The in vitro invasive phenotype was tested and quantified using a Transwell-Matrigel invasion assay. Cytokine secretion was measured using a BioLegend cytokine array. Results: TNBC CM greatly increased TNBC cell invasion in vitro and that treatment with the NAS PAMAM-G3 significantly inhibits this effect. Treatment of human monocytes (THP-1) with TNBC CM elicited a strong pro-inflammatory response with elevated levels of IL-8, IL-6, CCL2, and IL-1β. Other biologically immune responders including human PBMCs will be tested to determine the potential impact on the tumor immune microenvironment during tumorigenesis and treatment. Conclusions: To elucidate the mechanism by which this NAS works in these tumor settings, our lab has developed several PAMAM-G3 derivatives, including biotin, IR-, and near-IR fluorophore labeled molecules. These molecules will allow us to capture and characterize DAMPs and do in vivo live imaging experiments to gain insight into NAS PK/PD properties. This insight into NAS capabilities will enhance our understanding of metastatic progression and its interplay with the immune system. Moreover, these principles will aid in the development of novel of anti-metastatic therapies to improve TNBC patient outcomes.

scholarly journals Management Options in Triple-Negative Breast Cancer

2011 ◽  
Vol 5 ◽  
pp. BCBCR.S6562 ◽  
Author(s):  
Christina A. Minami ◽  
Debra U. Chung ◽  
Helena R. Chang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Chemotherapeutic Agents ◽  
Disease Entity ◽  
Management Options ◽  
Biological Specificity ◽  
Broad Overview

Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease's nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date.

scholarly journals Novel Aza-podophyllotoxin derivative induces oxidative phosphorylation and cell death via AMPK activation in triple-negative breast cancer

2020 ◽  
Author(s):  
Dhanir Tailor ◽  
Catherine C. Going ◽  
Angel Resendez ◽  
Vineet Kumar ◽  
Dhanya K. Nambiar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Phosphorylation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Aerobic Glycolysis ◽  
Chemotherapeutic Agents ◽  
Metabolic Reprogramming ◽  
Normal Cells ◽  
In Vivo Models

Abstract Background To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions work via indirectly activating AMP-activated protein kinase (AMPK) to alter cellular metabolism in favour of oxidative phosphorylation over aerobic glycolysis. The effect of these drugs is dependent on glycaemic and insulin conditions.  Therefore, development of small molecules, which can activate AMPK, irrespective of the energy state, may be a better approach for triple-negative breast cancer (TNBC) treatment. Methods Therapeutic effect of SU212 on TNBC cells was examined using in vitro and in vivo models. Results We developed and characterised the efficacy of novel AMPK activator (SU212) that selectively induces oxidative phosphorylation and decreases glycolysis in TNBC cells, while not affecting these pathways in normal cells.   SU212 accomplished this metabolic reprogramming by activating AMPK independent of energy stress and irrespective of the glycaemic/insulin state. This leads to mitotic phase arrest and apoptosis in TNBC cells. In vivo, SU212 inhibits tumour growth, cancer progression and metastasis. Conclusions SU212 directly activates AMPK in TNBC cells, but does not hamper glucose metabolism in normal cells. Our study provides compelling preclinical data for further development of SU212 for the treatment of TNBC.

scholarly journals Novel antibody–drug conjugates for triple negative breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592091598 ◽  
Author(s):  
Aiko Nagayama ◽  
Neelima Vidula ◽  
Leif Ellisen ◽  
Aditya Bardia
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Clinical Development ◽  
Antibody Drug Conjugate ◽  
Drug Conjugates ◽  
Anti Cancer ◽  
Late Stages ◽  
Antibody Drug

Triple negative breast cancer (TNBC) is a heterogenous subtype of breast cancer often associated with an aggressive phenotype and poor prognosis. Antibody–drug conjugate (ADC), comprising of a monoclonal antibody linked to a cytotoxic payload by a linker, is gaining increasing traction as an anti-cancer therapeutic. Emerging ADC drugs such as sacituzumab govitecan (IMMU-132) and trastuzumab deruxtecan (DS-8201a) are in late stages of clinical development for patients with metastatic breast cancer, including TNBC. In this article, we review and discuss the development and clinical application of ADCs in patients with advanced TNBC.

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