Enhanced Paclitaxel Efficacy to Suppress Triple-Negative Breast Cancer Progression Using Metronomic Chemotherapy with a Controlled Release System of ElectrospunPoly-D-L-Lactide-Co-Glycolide (PLGA) Nanofibers

Triple-negative breast cancer (TNBC) is highly aggressive and responds poorly to conventional chemotherapy. The challenge of TNBC therapy is to maximize the efficacies of conventional chemotherapeutic agents and reduce their toxicities. Metronomic chemotherapy using continuous low-dose chemotherapy has been proposed as a new treatment option, but this approach is limited by the selection of drugs. To improve antitumor therapeutic effects, we developed electrospun paclitaxel-loaded poly-D-L-lactide-co-glycolide (PLGA) nanofibers as a topical implantable delivery device for controlled drug release and site-specific treatment. The subcutaneously implanted paclitaxel-loaded nanofibrous membrane in mice was compatible with the concept of metronomic chemotherapy; it significantly enhanced antitumor activity, inhibited local tumor growth, constrained distant metastasis, and prolonged survival compared with intraperitoneal paclitaxel injection. Furthermore, under paclitaxel-loaded nanofiber treatment, systemic toxicity was low with a persistent increase in lean body weight in mice; in contrast, body weight decreased in other groups. The paclitaxel-loaded nanofibrous membranes provided sustained drug release and site-specific treatment by directly targeting and changing the tumor microenvironment, resulting in low systemic toxicity and a significant improvement in the therapeutic effect and safety compared with conventional chemotherapy. Thus, metronomic chemotherapy with paclitaxel-loaded nanofibrous membranes offers a promising strategy for the treatment of TNBC.

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Efficacy, Safety, and Tumor Marker Inhibition of Apatinib Combined with Conventional Chemotherapy Regimens for Patients with Advanced Triple-Negative Breast Cancer

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8720679 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Jianzhao Chen ◽

Lixia Feng ◽

Qinghua Sheng ◽

Lianna Li

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Specific Treatment ◽

Serum Levels ◽

Carbohydrate Antigen ◽

Conventional Group ◽

Conventional Chemotherapy ◽

Significant Difference ◽

E Cadherin

Objective. Triple-negative breast cancer (TNBC) is an aggressive disease with highly invasive nature and poor outcomes. Due to the absence of specific treatment strategies for this tumor subgroup, patients with TNBC are treated with conventional therapeutics, frequently leading to systemic relapse. In this study, we sought to investigate apatinib combined with conventional chemotherapy regimens in treating patients with advanced TNBC concerning the efficacy, safety, expressions of tumor markers, and patient survival. Methods. This is a prospective study including 150 cases of advanced TNBC who were randomly arranged into a conventional group and combined group, with 75 cases per group. The patients in the conventional group were treated with conventional chemotherapy, and those in the combined group were treated with apatinib combined with conventional chemotherapy. The peripheral blood was collected from each patient, and carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), and carbohydrate antigen 125 (CA125) were determined. The expressions of nuclear proliferation antigen marker (Ki67), β-catenin, and E-cadherin were determined in the biopsy collected from each patient. Results. The objective remission rate (ORR) and disease control rate (DCR) (41.33% and 81.33%) in the combined group were notably higher than those in the conventional group (29.33% and 68.00%) ( P < 0.05 ). After treatment, the serum levels of CEA, CA153, and CA125 and the expressions of Ki67 and β-catenin were declined, but the expression of E-cadherin was increased in both groups; the combined group exhibited lower serum levels of CEA, CA153, and CA125, and the expressions of Ki67 and β-catenin were concurrent with a higher expression of E-cadherin than the conventional group ( P < 0.05 ). No significant difference was noted between the two groups regarding the occurrence of adverse reactions ( P > 0.05 ). Improved progression-free survival (PFS) was observed in the combined group compared to the conventional group ( P < 0.05 . Conclusion. These findings suggest that apatinib combined with conventional chemotherapy regimens confers a prolonged PFS for treating patients with advanced TNBC.

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Abstract 17055: Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer

Circulation ◽

10.1161/circ.142.suppl_3.17055 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Anindita Das ◽

Sahak Hovsepian ◽

Sayantanee Das ◽

Arun Samidurai ◽

Adolfo G Mauro ◽

...

Keyword(s):

Breast Cancer ◽

Body Weight ◽

Tumor Growth ◽

Triple Negative Breast Cancer ◽

Mtor Inhibitor ◽

Triple Negative ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Chemotherapeutic Efficacy

Background: Doxorubicin (DOX) is a first-line anticancer drug for the treatment of triple negative breast cancer (TNBC). However, its dose-dependent delayed and progressive cardiotoxicity limits its therapeutic application. NovoMedix (NM922) is a novel dual mTOR inhibitor/AMPK activator that was shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. We investigated whether combination therapy with DOX and NM922 exhibits synergistic chemotherapeutic effect while mitigating DOX cardiotoxicity. Methods & Results: Tumors were generated in athymic female BALB/cAnNCr-nu/nu mice by implanting MDA-MB-231 cells into the rear right flank. Mice with tumors (volume≈200mm 3 ) were randomized into 6 groups and treated as follows: 1) Control (n=10); 2) DOX (3 mg/kg; i.p. twice weekly, total 15 mg/kg; n=10); 3) NM922 (25 mg/kg/d; p.o. n=5); 4) DOX+NM922 (25 mg/kg/d; p.o. n=15); 5) NM922 (100 mg/kg/d; p.o. n=5); 6) DOX+NM922 (100 mg/kg/d; p.o. n=15). Tumor size, body weight and cardiac function were assessed throughout the study. DOX alone, and to a significant extent when in combination with NM922 (25 mg/kg) reduced tumor growth compared to control. NM922 (100 mg/kg) with/without DOX significantly reduced tumor growth as compared to DOX alone (Fig A). DOX caused reduction in body weight and survival of tumor-bearing mice. NM922 did not prevent DOX-induced cachexia, but significantly improved survival in DOX-treated mice (Fig B). DOX treatment caused a significant decline in left ventricular ejection fraction compared to control over 3 weeks, which was ameliorated with NM922 (100 mg/kg) co-treatment (Fig C&D). Conclusion: Our results suggest that NM922 may potentiate the chemotherapeutic efficacy of DOX in TNBC, while mitigating its cardiotoxicity. Moreover, these findings advocate the potential efficacy of utilizing lower DOX dosages when combined with NM922, which would have significant clinical implications.

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Abstract 1989: Targeting Sin3-Pf1 complex: Novel site-specific epigenetic therapy for triple negative breast cancer

10.1158/1538-7445.am2015-1989 ◽

2015 ◽

Author(s):

Nidhi Bansal ◽

Joanna Wexler ◽

Yeon-jin Kwon ◽

Elena C. Gil ◽

Boris Leibovitch ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Epigenetic Therapy ◽

Site Specific

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Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

World Journal of Clinical Oncology ◽

10.5306/wjco.v8.i6.437 ◽

2017 ◽

Vol 8 (6) ◽

pp. 437-446 ◽

Cited By ~ 11

Author(s):

Connie Rabanal ◽

Rossana Ruiz ◽

Silvia Neciosup ◽

Henry Gomez

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Metronomic Chemotherapy

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A uPAR targeted nanoplatform with an NIR laser-responsive drug release property for tri-modal imaging and synergistic photothermal-chemotherapy of triple-negative breast cancer

Biomaterials Science ◽

10.1039/c9bm01495k ◽

2020 ◽

Vol 8 (2) ◽

pp. 720-738 ◽

Cited By ~ 1

Author(s):

Siming Yu ◽

Guanning Huang ◽

Riming Yuan ◽

Tianfeng Chen

Keyword(s):

Breast Cancer ◽

Drug Release ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Release Mechanism ◽

High Efficient ◽

Release Property ◽

Anticancer Mechanism ◽

Nir Laser

A multifunctional Ir complex(iii) loaded nanoplatform is designed for high efficient imaging and therapy of TNBC. The photothermal controlled Ir complex release mechanism and the synergistic anticancer mechanism are elucidated.

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