Therapy For Triple-negative Breast Cancer Research Articles

Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study

BackgroundBreast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments.MethodsWe conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).ResultsEach treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis.SignificanceThis in vivo study highlights TNBC’s metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.

A dual thermo/pH-sensitive hydrogel as 5-Fluorouracil carrier for breast cancer treatment.

Intelligent hydrogels are promising in constructing scaffolds for the controlled delivery of drugs. Here, a dual thermo- and pH-responsive hydrogel called PCG [poly (N-isopropyl acrylamide-co-itaconic acid)/chitosan/glycerophosphate (PNI/CS/GP)] was established as the carrier of 5-fluorouracil (5-FU) for triple-negative breast cancer (TNBC) treatment. The PCG hydrogel was fabricated by blending synthesized [poly (N-isopropyl acrylamide-co-itaconic acid), pNIAAm-co-IA, PNI] with CS in the presence of GP as a crosslinking agent. The interaction between PCG hydrogel compositions was characterized by Fourier transforms infrared, NMR spectroscopy, and scanning electron microscopy. The PCG hydrogel presented an interconnected and porous structure with similar pore size, rapid swelling/deswelling rate in response to both temperature and pH change, and biocompatibility, upon which it was proposed as a great drug carrier. 5-FU had a dual thermo- and pH-responsive controlled release behavior from the PCG hydrogel and displayed an accelerated release rate in an acidic pH environment than in a neutral pH condition. The application of 5-FU-loaded PCG hydrogel exhibited a more promoted anticancer activity than 5-FU against the growth of TNBC cells both in vitro and in vivo. The outcomes suggested that the PCG hydrogel could be an excellent platform for local drug-delivery systems in the clinical therapy of TNBC.

CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer

The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation. Notably, CDK4 depletion or long-term CDK4/6 inhibition confers resistance to apoptosis in TNBC cells. Mechanistically, CDK4 enhances mitochondria-endoplasmic reticulum contact (MERCs) formation, promoting mitochondrial fission and ER-mitochondrial calcium signaling, which are crucial for TNBC metabolic flexibility. Phosphoproteomic analysis identified CDK4’s role in regulating PKA activity at MERCs. In this work, we highlight CDK4’s role in mitochondrial apoptosis inhibition and suggest that targeting MERCs-associated metabolic shifts could enhance TNBC therapy.

Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.

Triple-negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, is characterized by the non-appearance of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Clinically, TNBC is marked by its low survival rate, poor therapeutic outcomes, high aggressiveness, and lack of targeted therapies. Over the past few decades, many clinical trials have been ongoing for targeted therapies in TNBC. Although some classes, such as Poly (ADP Ribose) Polymerase (PARP) inhibitors and immunotherapies, have shown positive therapeutic outcomes, however, clinical effects are not much satisfiable. Moreover, the development of drug resistance is the major pattern observed in many targeted monotherapies. The heterogeneity of TNBC might be the cause for limited clinical benefits. Hence,, there is a need for the potential identification of new therapeutic targets to address the above limitations. In this context, some novel targets that can address the above-mentioned concerns are emerging in the era of TNBC therapy, which include Hypoxia Inducible Factor (HIF-1α), Matrix Metalloproteinase 9 (MMP-9), Tumour Necrosis Factor-α (TNF-α), β-Adrenergic Receptor (β-AR), Voltage Gated Sodium Channels (VGSCs), and Cell Cycle Regulators. Currently, we summarize the ongoing clinical trials and discuss the novel therapeutic targets in the management of TNBC.

Triple-helix β-glucan-based self-assemblies, synthesis, characterization and anticarcinogenic effect.

Triple negative breast cancer (TNBC) seriously endangers women's life and health due to its high invasion and mortality. Reactive oxygen species (ROS) mediated tumor cells apoptosis is considered an effective anticancer approach. Herein, we designed a natural active triple helix β-Glucan (BFP) wrapped single walled carbon nanotubes (SWNTs)-loaded doxorubicin (DOX) self-assembly (BSD) via generating excess ROS to induce oxidative stress damage for TNBC therapy. BSD could directly consume glutathione (GSH) to promote ROS. In vitro results demonstrated that BSD exhibited obvious antitumor effects to breast cancer cells by promoting apoptosis. Un-targeted metabolomics under molecular level identified the specific metabolic targets and unveiled that BSD markedly disturbed multiple metabolic pathways, including purine metabolism, pentose phosphate pathway, glutathione metabolism pathways, amino sugar and nucleotide sugar metabolism and energy metabolism, led to the inhibition of DNA and RNA synthesis, the generation of ROS, the exacerbation of DNA damage, the disruption of cell membrane integrity and the decrease of ATP. In vitro and in vivo oxidative stress assays further verified that BSD significantly promoted intracellular oxidative stress and resulted in cell damage. This study provides theoretical basis for the development and screening of new drugs based on ROS therapy for TNBC.

Food-derived phytochemicals from functional food (Allium sativum) as VEGF-R1 inhibitors: A novel approach for triple-negative breast cancer therapy

Food-derived phytochemicals from functional food (Allium sativum) as VEGF-R1 inhibitors: A novel approach for triple-negative breast cancer therapy

Exploring the potential of Arbacia lixula coelomic fluid peptides as cell cycle and angiogenesis inhibitor for triple-negative breast cancer therapy: In silico study

Exploring the potential of Arbacia lixula coelomic fluid peptides as cell cycle and angiogenesis inhibitor for triple-negative breast cancer therapy: In silico study

Concurrent Amplification of Ferroptosis and Immune System Activation Via Nanomedicine-Mediated Radiosensitization for Triple-Negative Breast Cancer Therapy.

Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging. Here, pH-responsive DSPE-PEoz modified hollow Bi2Se3-RSL3/diABZi (DP-HBN/RA) nanomedicine is designed as a radiation sensitizer for efficient treatment of triple-negative breast cancer by simultaneously amplifying ferroptosis and immune system activation. DP-HBN/RA can efficiently concentrate X-ray radiation energy inside the tumor, thereby promoting precise ionizing radiation exposure in tumor cells to produce large amounts of reactive oxygen species (ROS), leading to lipid peroxidation-induced ferroptosis. Meanwhile, ferroptotic cell death is intensified through the inactivation of GPX4 by RSL3 released from DP-HBN/RA to acidic conditions in the tumor microenvironment. Additionally, DP-HBN/RA enhances RT efficacy to exacerbate unrepairable DNA damage and release DNA fragments that activate the cGAS-STING signal pathway, evoking a systematic immune response. Ingeniously, the released diABZi reinforces cGAS-STING activation to boost the immunology antitumor effect. This work links the induction of ferroptosis and the initiation of systematic immune response to achieve highly effective tumor suppression, which opens up new avenues for future treatments of refractory tumors.

A First Report of Docosahexaenoic Acid‐Clocked Polymer Enveloped Gold Nanoparticles: A Way to Precision Breast Cancer and Triple Negative Breast Cancer Therapy and Its Apoptosis Induction

ABSTRACTFunctionalized gold nanoparticles (GNPs) are extensively utilized in various disciplines due to their excellent bioactivity, biocompatibility, and extended drug half‐life, influenced by the ligands and size that are changed on surfaces. In this study, we successfully fabricated GNPs coated with ligands containing docosahexaenoic acid (DHA) and polyethylene glycol (PEG) clocked by a carboxyl group. These nanoparticles are referred to as MPA@GNPs‐PEG‐DHA. The cytotoxicity results demonstrate that MPA@GNPs‐PEG‐DHA exhibits superior cell selectivity, explicitly inhibiting the proliferation of breast cancerous cells than noncancerous cell lines. Apoptosis is involved in the reduction of cell proliferation by MPA@GNPs‐PEG‐DHA, as demonstrated clearly through many assays measuring apoptotic index, including AO/EB staining, DAPI, annexin V‐FITC staining, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) measurement. The efficacy of MPA@GNPs‐PEG‐DHA in inducing apoptosis was demonstrated by its inhibition of mitochondrial dysfunction by ROS. MPA@GNPs‐PEG‐DHA has the potential to improve the induction of apoptosis in breast cancerous cells.

CBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.

The MYC proto-oncogene is upregulated in >60% of triple-negative breast cancers (TNBCs), it can directly promote tumor cell proliferation, and its overexpression negatively regulates anti-tumor immune responses. For all these reasons, MYC has long been considered as a compelling therapeutic target. However, pharmacological inhibition of MYC function has proven difficult due to a lack of a drug-binding pocket. Here, we demonstrate that the potent abrogation of MYC gene transcription by CBL0137 induces immunogenic cell death and reduces proliferation in MYC-high but not in MYC-low TNBC in vitro. CBL0137 also significantly inhibited the in vivo growth of primary tumors in a human MYC-high TNBC xenograft model (MDA-MB-231). Moreover, CBL0137 inhibited the tumor growth of highly aggressive mouse 4T1.2 syngeneic TNBC model in immunocompetent mice by inhibiting the MYC pathway and inducing Type I interferon responses. Immune profiling of CBL0137-treated mice revealed significantly enhanced tumor-specific immune responses and increased proportions of tumor infiltrating effector CD8+ T cells, CD4+ T cells, and NK cells. CBL0137-induced immune activation also resulted in increased exhaustion of immune effector cells. In particular, NKG2A up-regulation on activated effector cells and of its ligand Qa-1b on tumors in vivo was identified as a possible immune evasive mechanism. Indeed, NKG2A blockade synergized with CBL0137 significantly inhibiting the in vivo growth of 4T1.2 tumors. Collectively, our findings provide the rationale supporting the exploitation of CBL0137-induced anti-tumor immunity in combination with NKG2A blockade to improve the treatment of TNBC expressing high levels of MYC.

Au@109Pd Core-Shell Nanoparticles Conjugated to Panitumumab for the Combined β--Auger Electron Therapy of Triple-Negative Breast Cancer.

Apart from HER2-positive, triple-negative breast cancer (TNBC) is the second most highly invasive type of breast cancer. Although TNBC does not overexpress HER2 receptors, it has been observed that EGFR protein expression is present in this specific type of tumor, making it an attractive target for immune and radiopharmaceutical treatments. In our current study, we used 109Pd (T1/2 = 13.7 h) in the form of a 109Pd/109mAg in vivo generator as a source of β- particles and Auger electrons in targeted radionuclide therapy for TNBC. 109Pd, obtained through neutron irradiation of the 108Pd target, was deposited onto 15 nm gold nanoparticles to form Au@109Pd core-shell nanoparticles, which were then conjugated to the panitumumab antibody. Au@109Pd-PEG-panitumumab nanoparticles were bound, internalized, and partially routed to the nucleus in MDA-MB-231 human breast cancer cells overexpressing EGFR receptors. The Au@109Pd-panitumumab radioconjugate significantly reduced the metabolic activity of MDA-MB-231 cells in a dose-dependent manner. In conclusion, we have found that Au@109Pd-PEG-panitumumab nanoparticles show potential as a therapeutic agent for combined β--Auger electron targeted radionuclide therapy of TNBC. The simultaneous emission of β-, conversion, and Auger electrons from the 109Pd/109mAg generator, similar to 161Tb conjugates, significantly enhances the therapeutic effect. The partial localization of these nanoparticles into the cell nucleus, provided by the panitumumab vector, ensures effective therapy with Auger electrons. This is particularly important for the treatment of drug-resistant TNBC cells.

Body composition as a novel biomarker of recurrence risk in patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) patients are at increased risk for recurrence compared to other subtypes of breast cancer. Previous evidence showed that adiposity may contribute to worsened cancer control. Current measures of obesity, such as body-mass index (BMI), are poor surrogates of adiposity, while visceral-to-subcutaneous adiposity ratio (VSR), which can be measured from routine computed tomography (CT) imaging, is a direct adiposity measure. We hypothesized that VSR is a stronger predictor of recurrence compared with BMI in patients with TNBC. This study includes 162 women with stage I-III TNBC who completed standard of care therapy. Measures of body composition, including VSR, visceral adiposity (VA), and subcutaneous adiposity (SA), were estimated using a semi-automated quantitative imaging tool on CT images of the abdomen at the level of L2-L3. Anthropometric measures included BMI and waist circumference and were obtained from CT images. Associations of adiposity measures and recurrence risk were assessed using Fine and Gray competing risk models with death as a competing risk and age at diagnosis and clinical disease stage as covariates. During a median follow-up time of 3.6 years, 55 patients had recurrence. The median BMI at baseline was 30.2 [Quartiles: 26.3-35.2]. Body composition was not associated with overall or locoregional recurrence. VSR was significantly associated with an increased risk of distant recurrence, with a subdistribution hazard ratio of 4.25 (95% CI: 1.06-17.02), p = 0.041. By contrast, BMI was not associated with any recurrence risk. Consistent with our hypothesis, VSR was associated with a significant risk of distant recurrence and therefore may be a prognostic biomarker. Future directions include interventions targeting VSR reduction among patients with TNBC and VSR-directed therapy modulation.

Advancements in clinical research and emerging therapies for triple-negative breast cancer treatment.

Triple-negative breast cancer (TNBC), defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression, is acknowledged as the most aggressive form of breast cancer (BC), comprising 15%-20% of all primary cases. Despite the prevalence of TNBC, effective and well-tolerated targeted therapies remain limited, with chemotherapy continuing to be the mainstay of treatment. However, the horizon is brightened by recent advancements in immunotherapy and antibody-drug conjugates (ADCs), which have garnered the U.S. Food and Drug Administration (FDA) approval for various stages of TNBC. Poly (ADP-ribose) polymerase inhibitors (PARPi), particularly for TNBC with BRCA mutations, present a promising avenue, albeit with the challenge of resistance that must be addressed. The success of phosphoinositide-3 kinase (PI3K) pathway inhibitors in hormone receptor (HR)-positive BC suggests potential applicability in TNBC, spurring optimism within the research community. This review endeavors to offer a comprehensive synthesis of both established and cutting-edge targeted therapies for TNBC. We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

HMGB3 Contributes to Anti-PD-1 Resistance by Inhibiting IFN-γ-Driven Ferroptosis in TNBC.

Our previous studies showed HMGB3 expression may correlate with immunotherapy efficacy in breast cancer patients. Here, we investigated whether HMGB3 overexpression has an impact on anti-PD-1 therapy in triple-negative breast cancer (TNBC) and its molecular mechanisms. Animal models were established to observe the effect of HMGB3 on sensitivity to anti-PD-1 treatment. Correlation of HMGB3 expression and ferroptosis preventive proteins in TNBC patients' tissues with anti-PD-1 therapy efficacy was analyzed. The impact of HMGB3 on IFN-γ (Interferon-gamma) inhibitory effects and signaling was examined in human TNBC cells where HMGB3 expression was knocked down using siRNA. Moreover, TNBC cells stably transfected with lentiviral vectors containing cDNA of HMGB3 were also used to confirm the effect of overexpression of HMGB3 on IFN-γ inhibitory effect and signaling. Effect of HMGB3 on IFN-γ-driven ferroptosis and ferroptosis-associated protein expression were also investigated. Correlation of HMGB3 and IRF1 and GPX4 expression in patient's cancer tissue were also investigated. Our results demonstrated that HMGB3 expression contributes to resistance to anti-PD-1 therapy in vivo. HMGB3 expression correlated with treatment efficacy of immunotherapy and survival in TNBC patients. HMGB3 silence decreased resistance of breast cancer cells to IFN-γ cytotoxic effect, while HMGB3 overexpression increased resistance of these cancer cells. HMGB3 silence increased STAT1 phosphorylation and IRF1 expression upon IFN-γ treatment compared with control. Overexpression of HMGB3 inhibited STAT1 phosphorylation and IFN-γ signaling in TNBC cells. Moreover, HMGB3 also increased STAT3 activation and had an effect of interaction between STAT1 and STAT3. HMGB3 overexpression decreased IFN-γ-driven ferroptosis in TNBC cells. HMGB3 increased ferroptosis-inhibitory proteins (SLC7A11, GPX4, and SLC3A2) expression in TNBC cells. Ferroptosis inhibition recovers resistance to anti-PD-1 therapy in vivo. Immunohistochemistry showed HMGB3 expression correlated with ferroptosis-associated proteins and IRF1 expression in breast cancer tissue. HMGB3 contributes to anti-PD-1 resistance by inhibiting IFN-γ-driven ferroptosis in TNBC which suggested HMGB3 is a potential co-target with anti-PD-1 therapy for TNBC.

Remodeling of tumour microenvironment: strategies to overcome therapeutic resistance and innovate immunoengineering in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) stands as the most complex and daunting subtype of breast cancer affecting women globally. Regrettably, treatment options for TNBC remain limited due to its clinical complexity. However, immunotherapy has emerged as a promising avenue, showing success in developing effective therapies for advanced cases and improving patient outcomes. Improving TNBC treatments involves reducing side effects, minimizing systemic toxicity, and enhancing efficacy. Unlike traditional cancer immunotherapy, engineered nonmaterial's can precisely target TNBC, facilitating immune cell access, improving antigen presentation, and triggering lasting immune responses. Nanocarriers with enhanced sensitivity and specificity, specific cellular absorption, and low toxicity are gaining attention. Nanotechnology-driven immunoengineering strategies focus on targeted delivery systems using multifunctional molecules for precise tracking, diagnosis, and therapy in TNBC. This study delves into TNBC's tumour microenvironment (TME) remodeling, therapeutic resistance, and immunoengineering strategies using nanotechnology.

A Magnetically Actuated MOF-Based Nanozyme for Intensified Induction of Ferroptosis and Immunogenic Cell Death Via Autophagy Blockade.

Nanozymes mimicking enzymes show great promise in anti-tumor therapy but are often limited by their low catalytic activity and lack of tumor specificity in hostile tumor microenvironments. This study develops a novel nanozyme, D/P@ZUCO, utilizing metal-organic frameworks (MOFs) with glutathione oxidase, peroxidase, and catalase-like activities. D/P@ZUCO is synthesized using ZnFe2O4 and NH2-UiO66 (Cu/Zr) through an in situ growth method, followed by loading with doxorubicin (DOX) and primaquine (PQ), and functionalization with oxidized hyaluronic acid (OHA). It efficiently catalyzes the conversion of hydrogen peroxide (H2O2) into hydroxyl radicals (·OH) and glutathione (GSH) into glutathione disulfide (GSSH), initiating ferroptosis in cancer cells. Additionally, the conversion of excess H2O2 into oxygen (O2) enhances the apoptosis effects of DOX. Importantly, the inhibition of autophagy by D/P@ZUCO exacerbates ferroptosis and immunogenic cell death (ICD), triggering a potent anti-tumor immune response. The targeted drug delivery of D/P@ZUCO is facilitated by magnetic guidance and interactions between OHA and CD44 receptors. D/P@ZUCO demonstrates effective cancer treatment by triggering multiple cell death pathways through a synergistic combination of enzymatic actions, serving as a paradigm for systemic activation of multiple enzymes in triple-negative breast cancer therapy.

Heterogeneity of tertiary lymphoid structures predicts the response to neoadjuvant therapy and immune microenvironment characteristics in triple-negative breast cancer.

Tertiary lymphoid structures (TLSs) impact cancer outcomes, including in triple-negative breast cancer (TNBC), where their role in immune modulation during neoadjuvant therapy (NAT) is underexplored. This study employed single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence (mIF) staining, and radiomic techniques to evaluate TLSs and the tumour microenvironment (TME) in TNBC patient samples before and after NAT. The presence of TLSs in TNBC was associated with B-cell maturation and T-cell activation. Compared with TLS-low TNBC, TLS-high TNBC showed significantly greater expression of immunoglobulin family genes (IGHM and IGHG1) in B cells and greater cytotoxicity of neoantigen-specific CD8 + T cells (neoTCR8). Additionally, mIF revealed notable differences between TLSs and the TME in TNBC. Although CD8 + T-cell levels do not predict the NAT response effectively, TLS maturity strongly correlated with better NAT outcomes and prognosis (P < 0.05). An imaging biomarker scoring system was also developed to predict TLS status and NAT efficacy. Our results demonstrated changes in TLSs and the TME in TNBC patients post-NAT. These findings confirm the predictive value of mature TLSs (mTLSs) and support the use of personalised immunotherapy based on post-NAT immune characteristics, thereby improving clinical outcomes.

Current progress and future trends of clinical trials of CAR-T cell therapy for triple-negative breast cancer

Current progress and future trends of clinical trials of CAR-T cell therapy for triple-negative breast cancer

Role of Harmaline in Inhibiting c-Myc, Altering Molecular Typing, and Promoting Apoptosis in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks effective targeted, endocrine therapeutic agents and the development of novel agents is costly and time-consuming. The objective of this study was to identify pharmaceuticals and natural products utilized in clinical practice that have the potential to inhibit the expression of Cellular-myelocytomatosis oncogene (c-Myc), based on a review of the current literature. The aim was to assess the effect of the specified drugs on c-Myc expression in TNBC cells, determine the most potent inhibitor, and evaluate its impact on TNBC cell proliferation, invasive migration, and apoptosis, as well as the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) at both the gene and protein levels. Explore its potential for treatment or adjuvant therapy for triple-negative breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify gene and protein expression levels. Flow cytometry was employed to measure cell proliferation and apoptosis, while the Transwell assay was utilized to assess cell invasion and migration. Harmaline emerged as the strongest inhibitor, significantly decreasing the expression of c-Myc at both the gene and protein levels in TNBC cells. It also inhibited cell proliferation, invasion, and migration while promoting apoptosis in TNBC cells. Additionally, there was a varying increase in the expression of ER and PR genes and proteins. While the expression of the HER-2 gene was elevated, there was no significant change in HER-2 protein levels. Notably, the expression of the phosphorylated HER-2 protein increased. Harmaline was found to promote apoptosis and inhibit cell proliferation, invasion, and migration in TNBC cells by targeting the inhibition of c-Myc. It also induced the re-expression of the ER, PR, and HER-2 genes, as well as the ER and PR proteins.

Innovative Nanomaterials for Targeting Hypoxia to Improve Treatment for Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a high rate of metastases, a short overall survival time, and a poor response to targeted therapy. Improving tumor hypoxia by lowering the oxygen consumption rate of breast tumor cells is a powerful strategy. A viable way to address this issue is to improve therapeutic efficacy by improving the effectiveness of radiation and overcoming drug resistance in TNBC treatment by controlling hypoxia in the tumor microenvironment. The failure of radiation and chemotherapy in TNBC is frequently caused by hypoxia. In TNBC therapy, novel nanomaterials are used for oxygen delivery or generation to affect the tumor microenvironment to improve the effects of ionizing radiation using nanoplatforms. One of the growing fields is novel nano-based drug delivery devices for hypoxic regions and hypoxia- inducible factor-1 (HIF1) targeted therapeutics. Biocompatible nanoparticles may be used in the treatment of TNBC patients in the clinic. Because of the rising market and competition, intellectual property rights (IPR), patents, and tactics may be critically considered. To better comprehend the current state of IPR and patents in cancer nanotechnology, this overview examines recent advances and sophisticated protection measures in this area.