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 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 Enhanced Anticancer Activity of Nanoformulation of Dasatinib against Triple-Negative Breast Cancer by Reduced Metabolic Degradation

2021 ◽  
Author(s):  
Fatemah Bahman ◽  
Valeria Pittalà ◽  
Mohamed Haider ◽  
Khaled Greish
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Triple Negative Breast Cancer ◽  
Tyrosine Kinases ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Response To Chemotherapy

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC, by lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is unresponsive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment but, despite an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA-dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA-dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management.

Co-loading of an anthracycline analogue Pirarubicin and Salinomycin in a 1:3 ratio into Quatramerbiodegradable polymeric nanoparticles synergistically inhibit growth of triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Surender Kharbanda ◽  
Anees Mohammad ◽  
Sachchidanand Tiwari ◽  
Neha Mehrotra ◽  
Sireesh Appajosyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancers ◽  
Mice Model ◽  
Single Drug ◽  
Tnbc Cell ◽  
Dual Drug

e15047 Background: Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and differ from other types of invasive breast cancers in that they grow and spread faster. TNBCs have limited treatment options and a worse prognosis. Therapy with anthracyclines considered to be one of the most effective agents in the treatment. Unfortunately, resistance to anthracycline therapy is very common due to drug efflux mediated by overexpression of ABC transporter. Pirarubicin (PIRA), an analogue of doxorubicin (DOX), is approved in Japan, Korea and China and is shown to be less cardiotoxic than DOX. Recent studies suggest that cancer stem cells (CSCs) play an important role in tumorigenesis and biology of TNBC. Targeting CSCs may be a promising, novel strategy for the treatment of this aggressive disease. Recent studies have shown that salinomycin (SAL) preferentially targets the viability of CSCs. Methods: SAL and PIRA were co-encapsulated in polylactic acid (PLA)-based block copolymeric nanoparticles (NPs) to efficiently co-deliver these agents to treat TNBC cells. Results: Generated SAL-PIRA co-encapsulated dual drug-loaded NPs showed an average diameter of 110 ± 7 nm, zeta potential of -12.5 mV and PDI of less than 0.25. Both of these anti-cancer agents showed slow and sustained release profile in non-physiological buffer (PBS, pH 7.4) from these dual drug-encapsulated NPs. Additionally, multiple ratios (PIRA:SAL = 3:1, 1:1, 1:3) were encapsulated to generate diverse dual drug-loaded NPs. The results demonstrate that, in contrast to 1:1 and 3:1, treatment of TNBC cells with 1:3 ratio of PIRA:SAL dual drug-loaded NPs, was associated with significant inhibition of growth in vitro in multiple TNBC cell lines. Interestingly, PIRA:SAL (1:3) was synergistic as compared to either SAL- or PIRA single drug-loaded NPs. The IC50 of PIRA and SAL in single drug-encapsulated NPs is 150 nM and 700 nM respectively in MDA-MB-468. Importantly, the IC50 of PIRA in dual drug-encapsulated NPs dropped down to 30 nM (5-fold). Similar results were obtained in SUM-149 TNBC cell line. Studies are underway to evaluate in vivo biological activity of PIRA:SAL (1:3) on tumor growth in a TNBC xenograft mice model. Conclusions: These results demonstrate that a novel dual drug-loaded NP formulation of PIRA and SAL in a unique ratio of 1:3 represents an approach for successful targeting of CSCs and bulk tumor cells in TNBC and potentially other cancer types.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

scholarly journals Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Karima Oualla ◽  
Loay Kassem ◽  
Lamiae Nouiakh ◽  
Lamiae Amaadour ◽  
Zineb Benbrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

scholarly journals Development of Targeted Therapy Therapeutics to Sensitize Triple-Negative Breast Cancer Chemosensitivity Utilizing Bacteriophage phi29 Derived Packaging RNA

2020 ◽  
Author(s):  
Long Zhang ◽  
Chaofeng Mu ◽  
Tinghong Zhang ◽  
Dejun Yang ◽  
Luhui Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Sirna Delivery ◽  
Growth Factor Receptor ◽  
Her2 Breast Cancer ◽  
Packaging Rna

Abstract Background: To date, triple-negative breast cancer (TNBC) treatment options are limited due to it lacks expression of receptors and are only available managed with chemotherapy. What's worse, TNBC is frequently developing resistance to chemotherapy. By using siRNA-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to HER2+ breast cancer development and chemoresistance. As is well-known, the instability, off-target effects, net negative charge, and hydrophobicity of siRNA hamper its’ in vivo utilization and clinical transformation. Thus, the development of a siRNA delivery system (DDS) with ultra-stability and specificity is demanded to address the predicament of siRNA delivery.Results: Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ of Phi29 DNA packaging motor. To targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote the sensitization of chemotherapy and impair angiogenesis in vivo. Conclusions: The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.

Triple-Negative Breast Cancer

2019 ◽  
Author(s):  
Diane M. Radford ◽  
Jame Abraham ◽  
Stephen R. Grobmyer
Keyword(s):  
Breast Cancer ◽  
African American Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Cancer Breast ◽  
Gene Testing ◽  
Visceral Metastases ◽  
Epidermal Growth

Triple-negative breast cancers (TNBCs), negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, account for 15 to 20% of all female breast cancers. TNBC is heterogeneous based on gene expression microarray, and identification of TNBC subtypes and their behavior has the potential to enable more targeted, neoadjuvant, and adjuvant interventions. TNBCs usually are higher grade (Nottingham score 3) and are more common in younger, Hispanic, and African American women. They are more aggressive, have an increased likelihood of distant disease and mortality, are larger at presentation, and are more likely to be associated with lymph node metastases. Patients with TNBC are at a higher risk for visceral metastases early in the course of the disease. Genetic risk evaluation is recommended for patients with TNBC diagnosed at or before 60 years of age. Surgical management may be influenced by gene testing results. Standard adjuvant chemotherapy is anthracycline or taxane based. This review contains 5 figures, 8 tables, and 51 references. Key Words: adjuvant, BRCA, chemotherapy, hormone receptor negative, neoadjuvant, genetics, triple-negative breast cancer, breast neoplasm.

scholarly journals Curcumin–Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer

Nanomaterials ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 884 ◽  
Author(s):  
Khaled Greish ◽  
Valeria Pittalà ◽  
Sebastien Taurin ◽  
Safa Taha ◽  
Fatemah Bahman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Copper Complex ◽  
Triple Negative ◽  
Cancer Survival ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Anti Cancer

Breast cancer is the most common cancer diagnosed among females worldwide. Although breast cancer survival has largely improved in the past 30 years, it remains highly heterogeneous in its response to treatment. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2). While TNBC may initially be responsive to chemotherapy, recurrence and subsequent high mortality rates are frequently reported. Studies have shown curcumin and its derivatives to be effective against TNBC cell lines in vitro. To improve its anti-cancer effects, we have synthesized Fe3+–curcumin (Fe–Cur3) and Cu2+–curcumin (CD) complexes and investigated them experimentally. Further, CD was encapsulated into a poly(styrene)-co-maleic acid (SMA) micelle to enhance its stability. We assessed the cytotoxicity of these formulations both in vitro and in vivo. SMA–CD demonstrated dose-dependent cytotoxicity and abolished TNBC tumor growth in vivo. The encapsulation of the curcumin–copper complex improved its anti-cancer activity without overt adverse effects in a murine model of TNBC. These results provide evidence and insights into the value of nanoformulations in enhancing drug-delivery and increasing the potential therapeutic efficacy of curcumin derivatives.

scholarly journals Disease-free Probability and Triple-Negative Breast Cancer

2012 ◽  
Vol 35 (1) ◽  
pp. 5-13
Author(s):  
Prakasit Chirappapha ◽  
Thongchai Sukarayothin ◽  
Yodying Wasuthit ◽  
Ronnarat Suvikapalornkul ◽  
Panuwat Lertsithichai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Free Probability ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients

Objective: To compare the probabilities of local recurrence and distant metastasis between women with triple-negative and non- triple negative breast cancers. Methods: Medical and pathological records of breast cancer patients treated between the years 2002 and 2006 were reviewed. Results: There were 256 patients with complete data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression determinations. There were 54 patients (21%) with triple-negative (ER-, PR-, HER2 -) cancers. Triple-negative patients were more likely to have larger tumors with higher histologic grade. The median fallow-up time was 4 years. The probabilities of local and distant recurrence were similar between the two groups of patients. Only two factors were independently and significantly associated with overall recurrence: tumor stage and tumor size. Conclusion: Triple-negative breast cancer did not have a higher risk for both local recurrence and distant metastasis when compared with non-triple negative cancer.

scholarly journals Current and emerging treatment options in triple-negative breast cancer

2011 ◽  
Vol 4 (1) ◽  
pp. 5
Author(s):  
Omer Dizdar ◽  
Kadri Altundag
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Histological Grade ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Immunohistochemical Analysis ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Chemotherapy Drugs

Triple-negative breast cancer is defined by the lack of estrogen receptor, progesterone receptor and HER2 expression with immunohistochemical analysis. Triplenegative breast cancers are poorly differentiated, characterized by high histological grade and occur at a younger age. Treatment options are limited as these tumors are naturally resistant to existing targeted therapies, i.e., endocrine treatment and trastuzumab. An improved understanding of the biology of TNBC has led to evaluation of DNA-damaging chemotherapy drugs and targeted agents, including poly (ADP-ribose) polymerase inhibitors, epidermal growth factor receptor inhibitors, angiogenesis inhibitors, etc., in the treatment of TNBC. This review focuses on outlining the current and emerging treatment options in patients with triple-negative breast cancer.

Sign in / Sign up

Export Citation Format

Share Document