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.

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