scholarly journals Abstract 4608: Colchicine binding site agents as potent tubulin inhibitors suppressing triple negative breast cancer

2019 ◽  
Author(s):  
Shanshan Deng ◽  
Hao Chen ◽  
Raisa Krutilina ◽  
Najah G. Albadari ◽  
Tiffany N. Seagroves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tubulin Inhibitors ◽  
Colchicine Binding Site

scholarly journals Abstract 4608: Colchicine binding site agents as potent tubulin inhibitors suppressing triple negative breast cancer

2019 ◽  
Author(s):  
Shanshan Deng ◽  
Hao Chen ◽  
Raisa Krutilina ◽  
Najah G. Albadari ◽  
Tiffany N. Seagroves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tubulin Inhibitors ◽  
Colchicine Binding Site

scholarly journals O-43 A KRAS microRNA binding site variant is a genetic marker of risk for triple negative breast cancer

2010 ◽  
Vol 8 (6) ◽  
pp. 16
Author(s):  
H.M. Heneghan ◽  
N. Miller ◽  
T. Paranjape ◽  
F.J. Slack ◽  
J.B. Weidhaas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Genetic Marker ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
O 43

scholarly journals Targeting Thymidylate Synthase Enhances the Chemosensitivity of Triple-Negative Breast Cancer Towards 5-FU-Based Combinatorial Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Nair Hariprasad Haritha ◽  
Akbar Nawab ◽  
Vinod Vijayakurup ◽  
Nikhil Ponnoor Anto ◽  
Vijayasteltar B. Liju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Triple Negative Breast Cancer ◽  
Thymidylate Synthase ◽  
Triple Negative ◽  
Therapeutic Index ◽  
Treatment Modalities ◽  
Combinatorial Therapy ◽  
Clinical Model

BackgroundThe ongoing treatment modalities for breast cancer (BC) primarily rely on the expression status of ER, PR and HER-2 receptors in BC tissues. Our strategy of chemosensitization provides new insights to counter chemoresistance, a major obstacle that limits the benefits of chemotherapy of mammary cancers.MethodsBy utilizing a murine breast cancer model employing NSG mice bearing orthotopic triple-negative breast cancer (TNBC) xenografts, we have evaluated the ability of phytochemical curcumin in chemosensitizing BC to 5-Fluorouracil (5-FU) chemotherapy and the differential modulations of cellular events in response to this strategy, independent of their receptor status.ResultsA significant synergistic antitumor potential was observed in the murine model with a sub-optimal dose treatment of 5-FU plus curcumin, as evaluated by a reduction in the tumor-related parameters. We authenticated the pivotal role of thymidylate synthase (TS) in regulating the 5-FU–curcumin synergism using the TNBC pre-clinical model. Our study also confirmed the pharmacological safety of this chemotherapeutic plus phytoactive combination using acute and chronic toxicity studies in Swiss albino mice. Subsequently, the molecular docking analysis of curcumin binding to TS demonstrated the affinity of curcumin towards the cofactor-binding site of TS, rather than the substrate-binding site, where 5-FU binds. Our concomitant in vivo and in silico evidence substantiates the superior therapeutic index of this combination.ConclusionThis is the first-ever pre-clinical study portraying TS as the critical target of combinatorial therapy for mammary carcinomas and therefore we recommend its clinical validation, especially in TNBC patients, who currently have limited therapeutic options.

Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation

2020 ◽  
Vol 17 (5) ◽  
pp. 682-695 ◽  
Author(s):  
Michael A. Arowosegbe ◽  
Oluwamuyiwa T. Amusan ◽  
Segun A. Adeola ◽  
Oluwatosin B. Adu ◽  
Israel A. Akinola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Free Energy ◽  
Binding Site ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Free Energy Calculations ◽  
Atp Binding ◽  
Energy Calculation ◽  
Atp Binding Site ◽  
Glide Docking

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many human tumors, particularly in Triple Negative Breast Cancer (TNBC) progression. Studies have revealed the crucial role of PAK4 in cell proliferation, anchorage-independent growth and cell migration among other hallmarks of cancer. Thus, PAK4 is an attractive target for anti-TNBC drug design and development. In our research, we used in silico methods to investigate the inhibitory potentials of kaempferol against PAK4 as compared with co-crystallized 4T6 and a standard PAK4 inhibitor-KPT-9274. The ligands were docked into the ATP-binding site of the target enzyme and post-docking validations were calculated. Results: In the molecular docking results, kaempferol had higher affinity than the standard KPT-9274. However, the SP and XP docking scores for the co-crystallized 4T6 were the highest. The analyses of the docking showed a favorable interaction between kaempferol and the catalytic-important aminoacyl residues, especially GLU396, LEU398 and ASP458 in the ATP-binding site of PAK4 when compared with what was obtained in the 4T6-PAK4 complex. Molecular mechanics based MM-GBSA was used to validate docking results. The free energy calculations revealed that kaempferol may have a favorable biological activity. Furthermore, the druggability of each ligand was assessed using the QikProp module and the SwissADME online tool. Kaempferol possessed a propitious drug-like property when compared to the standard ligands. Conclusions: We, therefore, put forward a logical argument that kaempferol can be further evaluated as a potential PAK4 inhibitor in TNBC.

VERU-111 as an Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer and Evaluation of Novel Tubulin Inhibitors for Cancer Therapy

2020 ◽  
Author(s):  
◽  
Shanshan Deng ◽  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Mortality Rates ◽  
Tubulin Inhibitor ◽  
Tubulin Inhibitors ◽  
Clinical Challenge ◽  
Approved Drugs ◽  
Fda Approved Drugs

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

Abstract 3029: A KRAS microRNA binding site polymorphism as a novel biomarker of risk in triple negative breast cancer

2010 ◽  
Author(s):  
Trupti S. Paranjape ◽  
Helen Heneghan ◽  
Cory Pelletier ◽  
Aaron Hoffman ◽  
Michael J. Kerin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Site ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
AJ Robles ◽  
L Du ◽  
S Cai ◽  
RH Cichewicz ◽  
SL Mooberry
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes ◽  
Therapeutic Leads

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

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