State of art of advanced triple negative breast cancer

Khosravi-Shahi, Parham; Cabezón-Gutiérrez, Luis; Salcedo, Maria Inmaculada Aparicio

doi:10.1111/tbj.13369

Cited by 30 publications

(21 citation statements)

References 24 publications

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“…Some studies have also demonstrated the effectiveness of combining chemotherapy with bevacizumab (monoclonal anti-vascular endothelial growth factor antibody) or with atezolizumab (monoclonal anti-programmed death ligand 1 (PD-L1) antibody) for metastatic TNBC. In addition to first-line therapy, there are still other options, such as the use of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, such as olaparib and talazoparib [62], and through immunotherapy, which includes pembrolizumab (humanized monoclonal antibody (mAb) against programmed cell death protein 1 (PD-1)) [63,64] and avelumab (human mAb against PD-L1), also for patients with metastatic TNBC [65].…”

Section: Bc Subtypesmentioning

confidence: 99%

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Araújo

Kerkhoff

Maciel

et al. 2021

Purinergic Signalling

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Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

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Section: Bc Subtypesmentioning

confidence: 99%

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Araújo

Kerkhoff

Maciel

et al. 2021

Purinergic Signalling

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“…Triple-negative breast cancer (TNBC) accounts for about 20% of BC cases (2). TNBC is a distinct subtype of BC characterized by aggressive phenotype, high recurrence rates, high visceral metastasis rate, and worse outcomes (3)(4)(5). Molecular heterogeneity is prominent in the TNBC subtype, and is reflected by the obvious prognostic and patient's sensitivity to chemotherapy treatment, which is the only available systemic therapy currently (1).…”

Section: Introductionmentioning

confidence: 99%

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

et al. 2020

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Gefitinib resistance in triple negative breast cancer (TNBC) is a growing important concern. Glutathione peroxidase 4 (GPX4) is a main regulator of ferroptosis, which is pivotal for TNBC cell growth. We investigated GPX4-mediated ferroptosis in gefitinib sensitivity in TNBC. Gefitinib resistant TNBC cells MDA-MB-231/Gef and HS578T/Gef were constructed and treated with lentivirus sh-GPX4 and ferroptosis inhibitor ferrostatin-1. GPX4 expression, cell viability and apoptosis were detected. Malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels were evaluated. The levels of ferroptosis-related proteins were detected. Subcutaneous tumor model was established in nude mice, and gefitinib was intraperitoneally injected to evaluate tumor growth, apoptosis, and Ki-67 expression. GPX4 was increased in gefitinib-resistant cells. After silencing GPX4, the inhibition rate of cell viability was increased, the limitation of colony formation ability was reduced, apoptosis rate was increased, and the sensitivity of cells to gefitinib was improved. After silencing GPX4, MDA and ROS production were increased, while GSH was decreased. Silencing GPX4 promoted ferroptosis. Inhibition of GPX4 promoted gefitinib sensitivity by promoting cell ferroptosis. In vivo experiments also revealed that inhibition of GPX4 enhanced the anticancer effect of gefitinib through promoting ferroptosis. Overall, inhibition of GPX4 stimulated ferroptosis and enhanced TNBC cell sensitivity to gefitinib.

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“…However, %10-20 of BC cases are ER-and give no signi cant response against hormonal or targeted therapy. Although surgery, radiotherapy and chemotherapy (olaparib, Talzenna, atezolizumab) combinations preferred for ER-BCs treatment, still new therapeutic agents needed to develop for triple negative breast cancer (TNBCs) therapy [3].…”

Section: Introductionmentioning

confidence: 99%

Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and MDA-MB-468 breast cancer cells

et al. 2021

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Purpose: The constitutive activation of STAT3 through receptor tyrosine kinases triggered breast cancer cell growth, and invasion-metastasis. Atiprimod impacts anti-proliferative, anti-carcinogenic effects in hepatocellular carcinoma, lymphoma, multiple myeloma via hindering the biological activity of STAT3. Dose-dependent atiprimod evokes rst autophagy as a survival mechanism and then apoptosis due to prolonged ER stress in pituitary adenoma cells. The therapeutic e ciency and mechanistic action of atiprimod in breast cancer cells have not been investigated yet. Thus, we aimed to modulate the pivotal role of ER stress in atiprimod-triggered apoptosis in MDA-MB-231 and MDA-MB-468 breast cancer cells.Results: Dose-and time-dependent atiprimod treatment inhibits cell viability and colony formation in MDA-MB-468 and MDA-MB-231 breast cancer cells. A moderate dose of atiprimod (2 mM) inhibited STAT3 phosphorylation at Tyr705 residue and also suppressed the total expression level of p65. In addition, nuclear localization of STAT1, 3 and NF-kB was prevented by atiprimod exposure in MDA-MB-231 and MDA-MB-468 cells. Atiprimod evokes PERK, BiP, ATF-4, CHOP upregulation, and PERK (Thr980), eIF2a (Ser51) phosphorylation's. However, atiprimod suppressed IRE1a-mediated Atg-3, 5, 7, 12 protein expressions and no alteration were observed on Beclin-1, p62 expression levels. PERK/eIF2a/ATF4/CHOP axis pivotal role in atiprimod-mediated G1/S arrest and apoptosis via Bak, Bax, Bim and PUMA upregulation in MDA-MB-468 cells. Moreover, atiprimod renders MDA-MB-231 more vulnerable to type I programmed cell death by plasmid-mediated increased STAT3 expression. Conclusion:Atiprimod induced prolonged ER stress-mediated apoptosis via both activating PERK/eIF2a/ATF4/CHOP axis and suppressing STAT3/NF-kB transcription factors nuclear migration in TBNC cells. HighlightsAtiprimod induced endoplasmic reticulum stress

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State of art of advanced triple negative breast cancer

Cited by 30 publications

References 24 publications

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and MDA-MB-468 breast cancer cells

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