Glutamine-β-cyclodextrin for targeted doxorubicin delivery to triple-negative breast cancer tumors via the transporter ASCT2

2019 ◽  
Vol 7 (35) ◽  
pp. 5363-5375 ◽  
Author(s):  
Ping Zhou ◽  
Xingmei Liang ◽  
Ce Zhou ◽  
Jiaqi Qin ◽  
Chunyu Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cyclodextrin Derivative ◽  
Doxorubicin Delivery

Novel cyclodextrin derivative, glutamine-β-cyclodextrin, is developed as DOX carrier to minimize its side effects via TNBC tumors addiction to glutamine.

Evaluation of Local Injection of Bevacizumab against Triple-Negative Breast Cancer Xenograft Tumors

2019 ◽  
Vol 25 (8) ◽  
pp. 862-870
Author(s):  
Xin Jiang ◽  
Qiao-Li Zhang ◽  
Tie-Gang Liu ◽  
Wei-Peng Zhao ◽  
Ming Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Matrix Metalloproteinase ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Local Delivery ◽  
Local Injection ◽  
Vegf Receptor ◽  
Protein Protein Interaction ◽  
Local Injections

Background and objective:Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors.Methods:Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated.Results:The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration.Conclusion:This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.

scholarly journals Triple Negative Breast Cancer: A review of common therapeutic Targets and Current Treatment options.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Daud Akhtar ◽  
Ahsen Chaudhry
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Cancer Du Sein ◽  
Triple Negative ◽  
Treatment Options ◽  
Cell Signalling ◽  
Effets Secondaires ◽  
Breast Cancer Chemotherapy

Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks ER, PR, and HER2 expression. It is characterized by poor prognosis and resistance to standard treatment forms for breast cancer. Chemotherapy is still currently the core neo-adjuvant treatment option for patients with TNBC, although it has mixed levels of efficacy on overall survival and many serious side effects. Platinum- based therapies have been used to treat TNBC in conjunction with chemotherapy, but they are not a widely effective treatment due to the heterogeneity of TNBC. For this reason, other novel approaches, particularly those which target molecular components involved in TNBC pathogenesis, are being investigated. Angiogenesis inhibitors, which include monoclonal antibodies or small molecules that inhibit VEGF, have been shown to improve progression-free survival, but have not demonstrated an impact on overall survival. PARP enzyme inhibitors, when combined with chemotherapy and carboplatin for the treatment of TNBC, have demonstrated a significant reduction in risk progression and mortality. However, the majority of PARP inhibitors are still in trials and their effectiveness in clini- cal settings has yet to be determined. Additional proposed targets for directed therapy against TNBC include cell signalling pathways involving EGFR or PI3K. Overall, issues such as treatment resistance and side effects are important challenges that must be overcome in order to enable improvements in patient prognosis and clinical impact. RÉSUMÉ Le cancer du sein triple négatif (CSTN) est un sous-type de cancer du sein auquel il manque les récepteurs d’œstrogènes (ER), les récepteurs de progestérone (PR) et l’expression de HER2. Il est caractérisé par un pronostic défavorable et une résistance aux traite- ments standards du cancer du sein. À l’heure actuelle, la chimiothérapie est encore l’option principale de traitement néoadjuvant pour les patients ayant le CSTN, bien qu’elle ait des niveaux variés d’efficacité sur la survie globale, ainsi que de nombreux effets secondaires sérieux. Les thérapies à base de platine ont été utilisées pour traiter le CSTN en conjonction avec la chimiothérapie, mais elles ne sont pas très efficaces étant donné l’hétérogénéité du CSTN. En raison de cela, d’autres approches novatrices, particulièrement celles qui ciblent les composantes moléculaires impliquées dans la pathogenèse du CSTN, font actuellement l’objet d’enquêtes. Les inhibiteurs de l’angiogenèse, dont les anticorps monoclonaux ou les petites molécules inhibant le VEGF, ont démontré la capacité d’améliorer la survie sans progression de la maladie, mais n’ont pas démontré d’impact sur la survie globale. Les inhibiteurs d’enzymes PARP, lorsque combinés avec la chimiothérapie et le carboplatine pour le traitement du CSTN, ont démontré une réduction significative du risque de progression et de la mortalité. Toutefois, la majorité des inhibiteurs PARP subissent encore des essais et leur efficacité clinique reste à être déterminée. D’autres cibles suggérées pour la thérapie dirigée contre le CSTN incluent les voies de signalisation impliquant le EGFR ou le PI3K. Dans l’ensemble, des problèmes tels la résistance au traitement et les effets secondaires sont des défis importants qui doivent être surmontés afin de permettre des améliorations au niveau du pronostic du patient et de l’impact clinique. 

Repurposing drugs as novel triple negative breast cancer therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Amiya Das ◽  
Pallavi Agarwal ◽  
Gaurav Kumar Jain ◽  
Geeta Aggarwal ◽  
Viney Lather ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Drug Development ◽  
Recurrence Rate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Cancer Therapeutics ◽  
Cytotoxic Activities ◽  
Repurposed Drugs

Background: Among all the types of breast cancer (BC), triple negative breast cancer (TNBC) is the most aggressive form having high metastasis and recurrence rate with limited treatment options. Conventional treatments such as chemotherapy and radiotherapy have lots of toxic side effects and also no FDA approved therapies are available till now. Repurposing of old clinically approved drugs towards various targets of TNBC is the new approach with lesser side effects and also leads to successful inexpensive drug development with less time consuming. Medicinal plants containg various phytoconstituents (flavonoids, alkaloids, phenols, essential oils, tanins, glycosides, lactones) plays very crucial role in combating various types of diseases and used in drug development process because of having lesser side effects. Objective: The present review focuses in summarization of various categories of repurposed drugs against multitarget of TNBC and also summarizes the phytochemical categories that targets TNBC singly or in combination with synthetic old drugs. Methods: Literature information was collected from various databases such as Pubmed, Web of Science, Scopus and Medline to understand and clarify the role and mechanism of repurposed synthetic drugs and phytoconstituents aginst TNBC by using keywords like “breast cancer”, “repurposed drugs”, “TNBC” and “phytoconstituents”. Results: Various repurposed drugs and phytochemicals targeting different signaling pathways that exerts their cytotoxic activities on TNBC cells ultimately leads to apoptosis of cells and also lowers the recurrence rate and stops the metastasis process. Conclusion: Inhibitory effects seen in different levels, which provides information and evidences to researchers towards drug developments process and thus further more investigations and researches need to be taken to get the better therapeutic treatment options against TNBC.

[10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models

2020 ◽  
Vol 43 (5) ◽  
pp. 915-929 ◽  
Author(s):  
Ana Carolina Baptista Moreno Martin ◽  
Rebeka Tomasin ◽  
Liany Luna-Dulcey ◽  
Angélica Elen Graminha ◽  
Marina Araújo Naves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Anticancer Activity ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Models

Targeted Drug Therapy to Overcome Chemoresistance in Triple-negative Breast Cancer

2020 ◽  
Vol 20 (8) ◽  
pp. 559-572
Author(s):  
Mamta Kumari ◽  
Praveen Thaggikuppe Krishnamurthy ◽  
Piyong Sola
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Cancer Subtype ◽  
Prevent Tumor Growth ◽  
Target Side

Triple-negative Breast Cancer (TNBC) is the most aggressive and prevailing breast cancer subtype. The chemotherapeutics used in the treatment of TNBC suffer from chemoresistance, dose-limiting toxicities and off-target side effects. As a result, conventional chemotherapeutics are unable to prevent tumor growth, metastasis and result in failure of therapy. Various new targets such as BCSCs surface markers (CD44, CD133, ALDH1), signaling pathways (IL-6/JAK/STAT3, notch), pro and anti-apoptotic proteins (Bcl-2, Bcl-xL, DR4, DR5), hypoxic factors (HIF-1α, HIF-2α) and drug efflux transporters (ABCC1, ABCG2 and ABCB1) have been exploited to treat TNBC. Further, to improve the efficacy and safety of conventional chemotherapeutics, researchers have tried to deliver anticancer agents specifically to the TNBCs using nanocarrier based drug delivery. In this review, an effort has been made to highlight the various factors responsible for the chemoresistance in TNBC, novel molecular targets of TNBC and nano-delivery systems employed to achieve sitespecific drug delivery to improve efficacy and reduce off-target side effects.

scholarly journals Cytotoxicity of Selenium Immunoconjugates against Triple Negative Breast Cancer Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3352 ◽  
Author(s):  
Soni Khandelwal ◽  
Mallory Boylan ◽  
Julian Spallholz ◽  
Lauren Gollahon
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Cancer Cell Growth

Within the subtypes of breast cancer, those identified as triple negative for expression of estrogen receptor α (ESR1), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), account for 10–20% of breast cancers, yet result in 30% of global breast cancer-associated deaths. Thus, it is critical to develop more targeted and efficacious therapies that also demonstrate less side effects. Selenium, an essential dietary supplement, is incorporated as selenocysteine (Sec) in vivo into human selenoproteins, some of which exist as anti-oxidant enzymes and are of importance to human health. Studies have also shown that selenium compounds hinder cancer cell growth and induce apoptosis in cancer cell culture models. The focus of this study was to investigate whether selenium-antibody conjugates could be effective against triple negative breast cancer cell lines using clinically relevant, antibody therapies targeted for high expressing breast cancers and whether selenium cytotoxicity was attenuated in normal breast epithelial cells. To that end, the humanized monoclonal IgG1 antibodies, Bevacizumab and Trastuzumab were conjugated with redox selenium to form Selenobevacizumab and Selenotrastuzumab and tested against the triple negative breast cancer (TNBC) cell lines MDA-MB-468 and MDA-MB-231 as well as a normal, immortalized, human mammary epithelial cell line, HME50-5E. VEGF and HER2 protein expression were assessed by Western. Although expression levels of HER2 were low or absent in all test cells, our results showed that Selenobevacizumab and Selenotrastuzumab produced superoxide (O2•−) anions in the presence of glutathione (GSH) and this was confirmed by a dihydroethidium (DHE) assay. Interestingly, superoxide was not elevated within HME50-5E cells assessed by DHE. The cytotoxicity of selenite and the selenium immunoconjugates towards triple negative cells compared to HME-50E cells was performed in a time and dose-dependent manner as measured by Trypan Blue exclusion, MTT assay and Annexin V assays. Selenobevacizumab and Selenotrastuzumab were shown to arrest the cancer cell growth but not the HME50-5E cells. These results suggest that selenium-induced toxicity may be effective in treating TNBC cells by exploiting different immunotherapeutic approaches potentially reducing the debilitating side effects associated with current TNBC anticancer drugs. Thus, clinically relevant, targeting antibody therapies may be repurposed for TNBC treatment by attachment of redox selenium.

Updated results of neoadjuvant chemotherapy with carboplatin AUC 6 and docetaxel 75 mg/m2 in triple-negative breast cancer (TNBC).

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 149-149 ◽  
Author(s):  
Peter Kern ◽  
Hans C. Kolberg ◽  
Anne Kalisch ◽  
Rainer Kimmig ◽  
Dirk Pott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Survival Data ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Surrogate Marker ◽  
Complete Response ◽  
Term Survival ◽  
Carboplatin Auc

149 Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis unless a pathological complete response (pCR) is achieved or almost achieved (near-pCR). Treatment of TNBC remains a challenge as some patients fail to respond to the use of standard anthracyclin-based chemotherapy regimens. Phenotypic and molecular similarities between TNBC and BRCA1-associated breast cancer suggest that TNBC may share the same sensitivity to platinum analogues as tumors associated with BRCA1. Methods: 30 patients with primary, unilateral, non-metastasized TNBC (majority of them cT1 or cT2, two cT4) had to be unsuitable for standard anthracycline-based chemotherapy. They received 6 cycles, respectively in two case sonly 5 cycles, of carboplatin AUC 6 and docetaxel 75 mg/m² q3w. Adverse effects were recorded according to CTCAE V4.07. Primary endpoint was pathological complete response (pCR) and near-pCR, secondary endpoint toxicity. Results: 70% (21/30) of patients had either a pathological complete response (55%; 15/27) or a near-complete response (20%; 6/30) - defined as pT1mic and ypT1a - both being associated with a good prognosis. Eight remaining patients had still good partial response, leaving only low residual cancer burden, which was specified as ypT1, in contrast only one ypT4 tumor. Treatment was well tolerated - grade IV toxicities were predominantly hematological side effects (especially concerning neutropenia) and in 2 cases grade IV edema and joint pain. Carboplatin dose reduction (to an AUC of 5) was required in 5 cases (because of limited renal function, hematological side effects or patient’s age). Conclusions: Our results demonstrate a high-anti-tumour activity of docetaxel 75mg/m² in combination with carboplatin AUC 6, promising high rates of tumour regression and pathological complete remission. The omission of exposure to anthracyclines in patients with considerable heart disease risks seems to be feasible with a good pCR-rate, the latter being a surrogate-marker for long-term survival. Survival data of this trial are currently being updated and will be presented on the Breast Cancer Symposium.

scholarly journals Effective in vitro delivery of paclitaxel by nanocargo of mesoporous polycaprolactone against triple negative breast cancer cells by minimalizing drug dose

RSC Advances ◽  
2020 ◽  
Vol 10 (40) ◽  
pp. 24095-24107 ◽  
Author(s):  
Himadri Medhi ◽  
Saratchandra Singh Khumukcham ◽  
Bramanandam Manavathi ◽  
Pradip Paik
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Drug Dose

Porous-PCL-nanocapsules-Taxol is an effective nanomedicine for the treatment of triple negative breast cancer which can reduce the extent of side effects also.

scholarly journals A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer

2021 ◽  
Author(s):  
Aditya Bardia ◽  
Sara A Hurvitz ◽  
Hope S Rugo ◽  
Adam Brufsky ◽  
Javier Cortes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
New England ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
The Body ◽  
Plain Language ◽  
Watery Stool ◽  
Patient Advocates

Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. Metastatic breast cancer means the breast cancer has spread to other parts of the body. Triple negative means the breast cancer does not have 3 common proteins on the cell surface called receptors. This is a summary of the ASCENT study, published in the New England Journal of Medicine in April 2021. This study compared Sacituzumab Govitecan with standard chemotherapy. Chemotherapy is a treatment that kills cancer cells or stops them from dividing. 529 people with mTNBC took part in the study across 7 countries. All who took part had already received 2 previous chemotherapies, which stopped working for their cancer. The study showed that patients who took Sacituzumab Govitecan lived longer than those who took a different chemotherapy while on the study. Tumors shrank in more patients who took Sacituzumab Govitecan than in patients who took chemotherapy. In general, patients who took Sacituzumab Govitecan experienced more side effects. This included low levels of a type of white blood cell known as neutrophils (neutropenia) and loose or watery stool (diarrhea). Use of supportive care lessened these side effects. This summary also includes insights and perspectives from 2 breast cancer patient advocates. ClinicalTrials.gov NCT number: NCT02574455 . To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here .

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