Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development

Costa, Ricardo; Shah, Ami N.; Santa-Maria, Cesar A.; Cruz, Marcelo; Mahalingam, Devalingam; Carneiro, Benedito A.; Chae, Young Kwang; Cristofanilli, Massimo; Gradishar, William J.; Giles, Francis J.

doi:10.1016/j.ctrv.2016.12.010

Cited by 151 publications

(105 citation statements)

References 99 publications

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“…As previous reports have shown that epidermal growth factor receptor (EGFR) expression is upregulated in TNBC and could be a potential therapeutic target (29,30), we investigated if CME could mediate the protein expression of EGFR. Western blot results showed that CME could significantly downregulate the protein expression of EGFR, in a dose-and time-dependent manner ( Figures 5A, 6A), providing some initial insight into its potential mechanistic activity.…”

Section: Cme Downregulated Expression Of Egfr In Tnbc Cellsmentioning

confidence: 99%

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

et al. 2020

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Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

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Section: Cme Downregulated Expression Of Egfr In Tnbc Cellsmentioning

confidence: 99%

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

et al. 2020

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“…Especially, the women under the age of 40 years old with TNBC has poor clinical outcomes and disproportionately higher prevalence (4). Nowadays, although chemotherapy is considered the main treatment approach for TNBC patients; followed by surgery and radiotherapy, the treatment effect is limited, and most patients occur disease progression in a relatively short time span (5).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of FEN1 Increases Arsenic Trioxide-Induced ROS Accumulation and Cell Death: Novel Therapeutic Potential for Triple Negative Breast Cancer

et al. 2020

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, which is very difficult to treat and commonly develops resistance to chemotherapy. The following study investigated whether the inhibition of Flap Endonuclease 1 (FEN1) expression, the key enzyme in the base excision repair (BER) pathway, could improve the anti-tumor effect of arsenic trioxide (ATO), which is a reactive oxygen species (ROS) inducer. Our data showed that ATO could increase the expression of FEN1, and the knockdown of FEN1 could significantly enhance the sensitivity of TNBC cells to ATO both in vitro and in vivo. Further mechanism studies revealed that silencing FEN1 in combination with low doses of ATO might increase intracellular ROS and reduce glutathione (GSH) levels, by reducing the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); elevating ROS leaded to apoptosis and p38 and JNK pathway activating. In conclusion, our study suggested the combination of FEN1 knockdown and ATO could induce TNBC cell death by promoting ROS production. FEN1 knockdown can effectively decrease the application concentrations of ATO, thus providing a possibility for the treatment of TNBC with ATO.

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“…One of the first identified targets of these growth inhibitors was the epidermal growth factor receptor (EGFR) that plays a vital role in the survival of cancer cells and developing multidrug resistance [22]. The effectiveness of the small molecule EGFR tyrosine kinase inhibitor like gefitinib is highly appreciated for the treatment of breast cancer; however, it failed to produce notable improvement in advance stages of breast cancer [23].…”

Section: Molecular Feature Of Breast Cancer Occurrence Progression mentioning

confidence: 99%

Herbal Remedies for Breast Cancer Prevention and Treatment

Laskar¹,

Lourembam²,

Mazumder³

2020

Medicinal Plants - Use in Prevention and Treatment of Diseases

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Breast cancer is among the most common type of cancer in women around the globe. Prevention of breast cancer is better than its treatment. Because of the molecular variation and complexity underlying breast cancer occurrence, its treatment by using chemotherapy and/or radiotherapy is very complicated and often leads to undesirable side effects. Plants and their extracts have been used for centuries for the treatment of almost every disease and breast cancer is not an exception. Herbal products can be trusted for cancer treatment because of their low toxicity. Besides, herbal remedies are easily accepted by the majority of woman suffering from breast cancer because of their easy availability and affordability. In the last decade, a large number of plants and their compounds were reported to show promising anticancerous effects against breast cancer cells in both in vivo and in vitro models. However, their beneficial effects on breast cancer treatment are still doubtful due to the lack of randomized clinical trials. This chapter is dedicated to reporting the potential of some herbal products for the prevention and/or treatment of breast cancer. Besides, it focused on the anticarcinogenic mechanism of those phytocompounds to report their potential chemotherapeutic role.

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Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development

Cited by 151 publications

References 99 publications

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

Inhibition of FEN1 Increases Arsenic Trioxide-Induced ROS Accumulation and Cell Death: Novel Therapeutic Potential for Triple Negative Breast Cancer

Herbal Remedies for Breast Cancer Prevention and Treatment

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