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Journal ArticleDOI

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

23 Jul 2021-Biomedicines (Multidisciplinary Digital Publishing Institute)-Vol. 9, Iss: 8, pp 876
TL;DR: In this paper, the authors discuss the possible treatment options for triple negative breast cancer based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development.
Abstract: Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.
Citations
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TL;DR: In this article , the authors highlighted the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases, focusing on anti-cancer, antioxidant, anti-inflammatory, antiangiogenesis, and apoptotic effects.

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TL;DR: Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects including anti-oxidant and anti-inflammatory effects as discussed by the authors.
Abstract: Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

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Journal ArticleDOI
TL;DR: In this article, the authors reviewed the current results of clinical trials testing and future directions for the field of PARP inhibitor development, and showed promising activity as a chemotherapeutic agent in BRCA1- or bRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer.
Abstract: Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer. This review covers the current results of clinical trials testing and future directions for the field of PARP inhibitor development.

21 citations

Journal ArticleDOI
Dan Xie, Saiyang Li, Tianqi Wu, Xuehui Wang, Lin Fang 
TL;DR: In this paper , the miR-181c/MAP4K4 signaling was shown to suppress triple negative breast cancer (TNBC) cells proliferation and migration, promoted TNBC cells apoptosis, and regulated the cell cycle.
Abstract: Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. Triple-negative breast cancer (TNBC) is known as a highly aggressive subtype of BC due to high rate of recurrence and metastasis, poor prognosis and lacking of effective targeted therapies. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA that mostly functioning to silence the target mRNAs. In this study, we found miR-181c-5p (miR-181c) was down-expressed in TNBC tissues and cell lines, whereas MAP4K4 was highly-expressed. Up-regulation of miR-181c inhibited TNBC cells proliferation and migration, promoted TNBC cells apoptosis and regulated the cell cycle by arresting cells in the G0/G1 cell phase, while depletion of miR-181c showed opposite effect. Importantly, miR-181c suppressed MAP4K4 expression at both mRNA and protein levels by directly targeting MAP4K4, thereby inhibiting the tumor-promoting effect of MAP4K4. This study is the first to demonstrate the miR-181c/MAP4K4 signaling in suppressing TNBC, providing a novel therapeutic target for TNBC.

10 citations

References
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TL;DR: The arsenal of nanocarriers and molecules available for selective tumour targeting, and the challenges in cancer treatment are detailed and emphasized.
Abstract: Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

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TL;DR: This work investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells and developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines.
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2,099 citations

Journal ArticleDOI
TL;DR: Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single‐agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression‐free survival.
Abstract: Background The poly(adenosine diphosphate–ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 (BRCA1/2). Methods We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician’s choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review. Results Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% c...

1,298 citations

Journal ArticleDOI
TL;DR: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among thosewho received placebo plusNeoadjuant chemotherapy.
Abstract: Background Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether ...

1,226 citations

Trending Questions (1)
Tnbc androgen type and targeted therapy ?

The paper does not specifically mention the androgen type in TNBC or targeted therapy for it. The paper discusses potential treatment options for TNBC based on various receptors and pathways, but androgen receptor is not mentioned. The paper focuses on poly-ADP ribose polymerase 1, vascular endothelial growth factor receptor, and epidermal growth factor receptor as potential targets.