scholarly journals Growth Inhibitory Efficacy of Chinese Herbs in a Cellular Model for Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (12) ◽  
pp. 1318
Author(s):  
Nitin T. Telang ◽  
Hareesh B. Nair ◽  
George Y. C. Wong
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Cancer ◽  
Unmet Need ◽  
Chinese Herbs ◽  
Stem Cell Population ◽  
Bax Protein ◽  
Growth Inhibitory ◽  
Long Term Treatment

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor-α progesterone receptor and human epidermal growth factor receptor-2. Treatment for this breast cancer subtype is restricted to multidrug chemotherapy and survival pathway-based molecularly targeted therapy. The long-term treatment options are associated with systemic toxicity, spontaneous and/or acquired tumor resistance and the emergence a of drug-resistant stem cell population. These limitations lead to advanced stage metastatic cancer. Current emphasis is on research directions that identify efficacious, naturally occurring agents representing an unmet need for testable therapeutic alternatives for therapy resistant breast cancer. Chinese herbs are widely used in traditional Chinese medicine in women for estrogen related health issues and also for integrative support for cancer treatment. This review discusses published evidence on a TNBC model for growth inhibitory effects of several mechanistically distinct nontoxic Chinese herbs, most of them nutritional in nature, and identifies susceptible pathways and potential molecular targets for their efficacy. Documented anti-proliferative and pro-apoptotic effects of these herbs are associated with downregulation of RB, RAS, PI3K, and AKT signaling, modulation of Bcl-2/BAX protein expressions and increased caspase activity. This review provides a proof of concept for Chinese herbs as testable alternatives for prevention/therapy of TNBC.

scholarly journals Identifying Biomarkers to Pair with Targeting Treatments within Triple Negative Breast Cancer for Improved Patient Stratification

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1864 ◽  
Author(s):  
Holly Tovey ◽  
Maggie Chon U. Cheang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
High Throughput Sequencing ◽  
Triple Negative ◽  
Treatment Options ◽  
Unmet Need ◽  
Growth Factor Receptor ◽  
Parp Inhibitors ◽  
Genetic Features ◽  
The Uk

The concept of precision medicine has been around for many years and recent advances in high-throughput sequencing techniques are enabling this to become reality. Within the field of breast cancer, a number of signatures have been developed to molecularly sub-classify tumours. Notable examples recently approved by National Institute for Health and Care Excellence in the UK to guide treatment decisions for oestrogen receptors (ER)+ human epidermal growth factor receptor 2 (HER2)- patients include Prosigna® test, EndoPredict®, and Oncotype DX®. However, a population of still unmet need are those with triple negative breast cancer (TNBC). Accounting for 15–20% of patients, this population has comparatively poor prognosis and as yet no targeted treatment options. Studies have shown that some patients with TNBC respond favourably to DNA damaging drugs (carboplatin) or agents which inhibit DNA damage response (poly ADP ribose polymerase (PARP) inhibitors). Known to be a heterogeneous population, there is a need to identify further TNBC patients who may benefit from these treatments. A number of signatures have been identified based on association with treatment response or specific genetic features/pathways however many of these were not restricted to TNBC patients and as of yet are not common practice in the clinic.

scholarly journals Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Neng Wang ◽  
Gulizeba Muhetaer ◽  
Xiaotong Zhang ◽  
Bowen Yang ◽  
Caiwei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Late Phase ◽  
Breast Cancer Metastasis ◽  
Chinese Herbs ◽  
Caveolin 1 ◽  
Sanguisorba Officinalis

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments—including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection—validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

scholarly journals Expression of GATA3 in MDA-MB-231 Triple-negative Breast Cancer Cells Induces a Growth Inhibitory Response to TGFß

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61125 ◽  
Author(s):  
Isabel M. Chu ◽  
Wei-Chu Lai ◽  
Olga Aprelikova ◽  
Lara H. El Touny ◽  
Hosein Kouros-Mehr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Inhibitory Response ◽  
Growth Inhibitory

scholarly journals Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer

2020 ◽  
Author(s):  
Karen E Skinner ◽  
Amin Haiderali ◽  
Min Huang ◽  
Lee S Schwartzberg
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Free Survival ◽  
Regression Methods ◽  
Kaplan Meier ◽  
Community Oncology

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan–Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African–American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

scholarly journals Real-world treatment patterns and effectiveness outcomes in patients with early-stage triple-negative breast cancer

2021 ◽  
Author(s):  
Amin Haiderali ◽  
Whitney C Rhodes ◽  
Santosh Gautam ◽  
Min Huang ◽  
Jan Sieluk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Real World ◽  
Triple Negative ◽  
Cox Regression ◽  
Early Stage ◽  
Unmet Need ◽  
Complete Response ◽  
Treatment Patterns ◽  
Neoadjuvant Systemic Therapy

Background: This retrospective, observational study examined real-world treatment patterns and effectiveness outcomes in 450 patients with stage II–IIIB early-stage triple-negative breast cancer treated in the community oncology setting. Methods: Kaplan–Meier methods were used to evaluate event-free survival (EFS), time to recurrence and overall survival (OS). Cox regression models were used to evaluate predictors of EFS and OS by pathological complete response (pCR) status. Results: Among patients receiving neoadjuvant systemic therapy only, pCR was a predictor of EFS and OS. Conclusion: These results highlight the unmet need for therapies that improve outcomes for patients with early-stage triple-negative breast cancer including increasing rates of pCR among patients receiving neoadjuvant therapy.

scholarly journals RNF8–CDH1 Co-Expression Predicts Clinical Benefit of Chemoradiotherapy in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 (7) ◽  
pp. 655
Author(s):  
Chieh-Ni Kao ◽  
Sin-Hua Moi ◽  
Ming-Feng Hou ◽  
Chi-Wen Luo ◽  
Fang-Ming Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Unmet Need ◽  
Ring Finger ◽  
High Index ◽  
Anti Cancer ◽  
Suitable Treatment

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and exhibits an overall poor outcome. Due to the lack of targeted therapy, conventional systemic chemotherapy has been the main strategy for the treatment of TNBC. Further evidence has shown that combining radiation with chemotherapy is also a suitable treatment based on DNA repair deficiencies in patients with TNBC. However, the preferred treatment for metastatic TNBC remains unclear. Therefore, identification of biomarkers is an unmet need in personalized therapy for TNBC. RNF8 (ring finger protein 8) is a ubiquitin ligase implicated in TNBC metastasis; however, its role in TNBC pathogenesis is unclear. The purpose of the present study was to investigate the roles of the RNF8–CDH1(Cadherin 1) axis in node-positive TNBC patients. We found that the RNF8high/CDH1low index was significantly higher in patients with TNBC than in patients without TNBC. Furthermore, patients with an RNF8high/CDH1low index displayed poorer outcomes than those with an RNF8low-medium/CDH1medium-high index. Notably, as compared to patients with an RNF8low-medium/CDH1medium-high index, those with an RNF8high/CDH1low index had a poorer survival rate with chemotherapy treatment alone. The combination of radiation and chemotherapy resulted in a better survival rate than chemotherapy alone in patients with an RNF8high/CDH1low index. Taken together, the RNF8high/CDH1low index not only functions as a prognostic and therapeutic marker but may also act as a target in the development of anti-cancer agents for patients with TNBC.

scholarly journals Growth Inhibitory Efficacy of Tabebuia Avellanedae in a Model for Triple Negative Breast Cancer

2021 ◽  
pp. 203-209
Author(s):  
Nitin T Telang ◽  
Hareesh B Nair ◽  
George YC Wong
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cell Cycle Progression ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Fold Increase ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Long Term Treatment

Background: Tabebuia avellanedae (TA) is a tree that is indigenous to the Amazon rainforest. The experiments in the present study were designed to examine the inhibitory effects of TA, and to identify mechanistic targets for its efficacy in the estrogen-α receptor (ER-α), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) negative MDA-MB-231 model for triple negative breast cancer (TNBC). Methods: Non-fractionated aqueous extract from the inner bark of TA was used in the experiments. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression, and expressions of relevant regulatory proteins represented quantitative end points. Results: Long-term treatment for 21 days with the maximum cytostatic concentration of 2.5% TA resulted in a 90% inhibition (P=0.014) in AI colony number. Short-term treatment for 2 days with 1.0% TA (IC50) resulted in about a 1.3 fold increase (P=0.014) in G1: S+G2/M ratio, about a 1.48 fold increase (P=0.010) in the sub G0 (apoptotic) cells and about a 3.2 fold increase (P=0.014) in the pro-apoptotic caspase 3/7 activity. Mechanistically, the short-term treatment with 2.5% TA decreased Cyclin D1 expression by about 83.3%, and pRB expression by about 73.3%. Conclusion: TNBC represents an aggressive cancer notable for its resistance to conventional and targeted therapy. Non-toxic natural substances may represent testable alternatives. This study identifies potential mechanistic leads for TA as a novel naturally occurring testable alternative for secondary prevention/therapy of TNBC, and validates a novel mechanistic approach to evaluate efficacious non-toxic phytochemicals and herbs as testable alternatives against therapy resistant breast cancer.

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