Targeting of breast cancer with non-oncology drugs – possible novel therapeutic option for triple-negative breast cancer.

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

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Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis

Cancers ◽

10.3390/cancers13153871 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3871

Author(s):

Emma Rodriguez ◽

Guangsheng Pei ◽

Sang T. Kim ◽

Alexis German ◽

Prema Robinson

Keyword(s):

Breast Cancer ◽

Flow Cytometry ◽

Cell Line ◽

Pc12 Cells ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Therapeutic Option ◽

Neuronal Cell ◽

Receptor Antagonism ◽

Tnbc Cell

Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC.

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BikDDA, a Mutant of Bik with Longer Half-Life Expression Protein, Can Be a Novel Therapeutic Gene for Triple-Negative Breast Cancer

PLoS ONE ◽

10.1371/journal.pone.0092172 ◽

2014 ◽

Vol 9 (3) ◽

pp. e92172 ◽

Cited By ~ 4

Author(s):

Shiping Jiao ◽

Minqing Wu ◽

Feng Ye ◽

Hailin Tang ◽

Xinhua Xie ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Half Life ◽

Triple Negative ◽

Therapeutic Gene ◽

Novel Therapeutic

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Ganglioside GD2: a novel therapeutic target in triple‐negative breast cancer

Annals of the New York Academy of Sciences ◽

10.1111/nyas.14700 ◽

2021 ◽

Author(s):

Claire Shao ◽

Vivek Anand ◽

Michael Andreeff ◽

Venkata Lokesh Battula

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Therapeutic Target ◽

Triple Negative ◽

Ganglioside Gd2 ◽

Novel Therapeutic

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CBP/β-Catenin/FOXM1 Is a Novel Therapeutic Target in Triple Negative Breast Cancer

Cancers ◽

10.3390/cancers10120525 ◽

2018 ◽

Vol 10 (12) ◽

pp. 525 ◽

Cited By ~ 9

Author(s):

Alexander Ring ◽

Cu Nguyen ◽

Goar Smbatyan ◽

Debu Tripathy ◽

Min Yu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Drug Resistance ◽

Triple Negative Breast Cancer ◽

Therapeutic Target ◽

Triple Negative ◽

Creb Binding Protein ◽

Novel Therapeutic

Background: Triple negative breast cancers (TNBCs) are an aggressive BC subtype, characterized by high rates of drug resistance and a high proportion of cancer stem cells (CSC). CSCs are thought to be responsible for tumor initiation and drug resistance. cAMP-response element-binding (CREB) binding protein (CREBBP or CBP) has been implicated in CSC biology and may provide a novel therapeutic target in TNBC. Methods: RNA Seq pre- and post treatment with the CBP-binding small molecule ICG-001 was used to characterize CBP-driven gene expression in TNBC cells. In vitro and in vivo TNBC models were used to determine the therapeutic effect of CBP inhibition via ICG-001. Tissue microarrays (TMAs) were used to investigate the potential of CBP and associated proteins as biomarkers in TNBC. Results: The CBP/ß-catenin/FOXM1 transcriptional complex drives gene expression in TNBC and is associated with increased CSC numbers, drug resistance and poor survival outcome. Targeting of CBP/β-catenin/FOXM1 with ICG-001 eliminated CSCs and sensitized TNBC tumors to chemotherapy. Immunohistochemistry of TMAs demonstrated a significant correlation between FOXM1 expression and TNBC subtype. Conclusion: CBP/β-catenin/FOXM1 transcriptional activity plays an important role in TNBC drug resistance and CSC phenotype. CBP/β-catenin/FOXM1 provides a molecular target for precision therapy in triple negative breast cancer and could form a rationale for potential clinical trials.

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