Drug-resistant Breast Cancer Research Articles

Triggered ferroptotic albumin-tocopherol nanocarriers for treating drug-resistant breast cancer

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

Effects of BYL-719 (alpelisib) on human breast cancer stem cells to overcome drug resistance in human breast cancer.

Breast cancer continues to be a major health concern and is currently the most commonly diagnosed cancer worldwide. Relapse, metastasis, and therapy resistance are major clinical issues that doctors need to address. We believe BYL-719, which is PI3 kinase p110а inhibitor, could also inhibit the breast cancer stem cell phenotype and epithelial-to-mesenchymal transition (EMT). In addition to the PI3K/AKT signaling pathway, BYL-719 can also inhibit essential cancer-related signaling pathways, all of which would ultimately act on the microenvironment of cancer stem cells, which is quite complicated and regulates the characteristics of tumors. These include the stemness and resistance of malignant tumors, plasticity of cancer stem cells, and anti-apoptotic features. A three-dimensional (3D) mammosphere culture method was used in vitro to culture and collect breast cancer stem cells (BCSCs). MTT, clonogenic, and cell apoptosis assays were used to detect cell viability, self-renewal, and differentiation abilities. A sphere formation assay under 3D conditions was used to detect the mammophore inhibition rate of BYL-719. The subpopulation of CD44+CD24- was detected using flow cytometry analysis while EMT biomarkers and essential signaling pathways were detected using western blotting. All the data were analyzed using GraphPad Prism 9 software. BCSC-like cells were obtained by using the 3D cell culture method in vitro. We confirmed that BYL-719 could inhibit BCSC-like cell proliferation in 3D cultures and that the stemness characteristics of BCSC-like cells were inhibited. The PI3K/AKT/mTOR signaling pathway could be inhibited by BYL-719, and the Notch, JAK-STAT and MAPK/ERK signaling pathways which have crosstalk in the tumor microenvironment (TME) are also inhibited. By comparing eribulin-resistant breast cancer cell lines, we confirmed that BYL-719 could effectively overcome drug resistance. The 3D cell culture is a novel and highly effective method for enriching BCSCs in vitro. Furthermore, the stemness and EMT of BCSCs were inhibited by BYL-719 by acting on various signaling pathways. Finally, we believe that drug resistance can be overcome by targeting the BCSCs. Conjugation of BYL-719 with other anti-neoplastic agents may be a promising treatment for this in clinic.

8523 An Unconventional Estrogen Receptor Conformation Induces SUMO Expression In Breast Cancer Cells

Abstract Disclosure: G.R. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: None. An Unconventional Estrogen Receptor Conformation Induces SUMO Expression in Breast Cancer Cells Govinda Hancock, Kristen Young, Geoffrey L. Greene, Sean W. Fanning Competitive allosteric regulators, selective estrogen receptor modulators (SERMs)/degraders (SERDs) differentially manipulate receptor structure to treat and prevent metastatic breast cancers. However, their utility is limited by the ∼40% rate of disease progression due to acquired therapy resistance. In this study, a new SERM based on a tetrahydro-6-isoquinoline (T6I) scaffold reveals the relationship between ERα conformation and therapeutic transcriptional pathways in drug-resistant breast cancers. Optimization of structure-activity relationships produced unique lead compound that engages transcriptional programs similar to the clinically approved SERD fulvestrant. Notably, both drugs induce the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to the pathogenic hormone 17β-estradiol. SUMOylation is a post-translational modification affecting protein-protein interactions, localization, stability and functional properties. High expression of SUMO1 is associated with better patient prognosis in ERα+ disease. SUMOylation in breast cancer will be elucidated through understanding how it’s induced, its structural basis, and its role in therapeutic response of antiestrogen treatments. Presentation: 6/3/2024

Development of a polygenic score predicting drug resistance and patient outcome in breast cancer

Gene expression profiles of hundreds of cancer cell-lines and the cell-lines’ response to drug treatment were analyzed to identify genes whose expression correlated with drug resistance. In the GDSC dataset of 809 cancer cell lines, expression of 36 genes were associated with drug resistance (increased IC50) to many anti-cancer drugs. This was validated in the CTRP dataset of 860 cell lines. A polygenic score derived from the correlation coefficients of the 36 genes in cancer cell lines, UAB36, predicted resistance of cell lines to Tamoxifen. Although the 36 genes were selected from cell line behaviors, UAB36 successfully predicted survival of breast cancer patients in three different cohorts of patients treated with Tamoxifen. UAB36 outperforms two existing predictive gene signatures and is a predictor of outcome of breast cancer patients independent of the known clinical co-variates that affect outcome. This approach should provide promising polygenic biomarkers for resistance in many cancer types against specific drugs.

Ionizable Drugs Enable Intracellular Delivery of Co-Formulated siRNA.

Targeting complementary pathways in diseases such as cancer can be achieved with co-delivery of small interfering ribonucleic acid (siRNA) and small molecule drugs; however, current formulation strategies are typically limited to one, but not both. Here, ionizable small molecule drugs and siRNA are co-formulatedin drug-rich nanoparticles. Ionizable analogs of the selective estrogen receptor degrader fulvestrant self-assemble into colloidal drug aggregates and cause endosomal disruption, allowing co-delivery of siRNA against a non-druggable target. siRNA is encapsulated in lipid-stabilized, drug-rich colloidal nanoparticles where the ionizable lipid used in conventional lipid nanoparticles is replaced with an ionizable fulvestrant analog. The selection of an appropriate phospholipid and formulation buffer enables endocytosis and potent reporter gene knockdown in cancer cells. Importantly, siRNA targeting cyclin E1 is effectively delivered to drug-resistant breast cancer cells, demonstrating the utility of this approach. This strategy opens the possibility of using ionizable drugs to co-deliver RNA and ultimately improve therapeutic outcomes.

Antisense oligonucleotide facilitate the photothermal therapy of Mxene-based nanoplatform for drug-resistant breast cancer

Breast cancer has become the most common form of cancer worldwide. Chemotherapy failure, primarily due to drug resistance, necessitates the development of new therapeutic strategies. In this study, ultrathin Ti3C2 nanosheets are utilized as photothermal agents and nanocarriers. We developed a multifunctional Ti3C2-based nanoplatform (214.7 nm) through layer-by-layer absorption of HSP90 antisense oligonucleotide (ASO) and doxorubicin (DOX), with surface modification using hyaluronic acid (HA). In a simulated acidic tumor microenvironment in vitro, 90 % of the drug was released within 36 hours. Additionally, Under 808 nm irradiation (2.0 W/cm²), MCF-7/ADM cell viability assays revealed the following results: HA-Ti3C2 (57 %), HA-Ti3C2@ASO (HT@A) (41 %), and HA-Ti3C2@ASO/DOX (HT@AD) (26 %), which shown the synergistic inhibitory effects of this multifunctional nanoplatform. Herein, this nanosystem exhibits enhanced biocompatibility, superior photothermal performance, and stimuli-responsive drug release behavior, making it a promising candidate for effective inhibition of cancer cell proliferation and migration.

Kalata B1 Enhances Temozolomide Toxicity to Glioblastoma Cells.

Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin. We analyzed naturally occurring and synthetic cyclotides (Cycloviolacin O3, Cycloviolacin O19, natural Kalata B1, synthetic Kalata B1, and Vitri E) alone and in co-exposure treatments with the drug temozolomide (TMZ) in human glioblastoma cells. The cyclotides were identified by UPLC-PDA and HPLC-UV. The synthetic Kalata B1 sequence was verified with orbitrap LC-MS, and structural confirmation was provided by NMR spectroscopy. The cyclotides displayed dose-dependent cytotoxicity (IC50 values 2.4-21.1 µM) both alone and as chemosensitizers of U-87 MG and T 98 cells to TMZ. In fact, a 16-fold lower concentration of TMZ (100 µM) was needed for significant cytotoxicity in U-87 MG cells co-exposed to synthetic Kalata B (0.5 µM). Similarly, a 15-fold lower concentration of TMZ (75 µM) was required for a significant reduction in cell viability in T 98 cells co-exposed to synthetic Kalata B1 (0.25 µM). Kalata B1 remained stable in human serum stability assays. The data support the assertion that cyclotides may chemosensitize glioblastoma cells to TMZ.

New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells.

Mitochondria are considered as promising targets for cancer treatment. In the present study, triphenyl phosphonium cationic group-conjugated fisetin (mito-fisetin) was synthesized, and its anticancer activity was investigated in several cellular models of estrogen receptor (ER)-positive breast cancer in vitro and in vivo in proliferating and tamoxifen-promoted senescent states. Mito-fisetin, when used at low micromolar concentrations, stimulated the dissipation of mitochondrial membrane potential and oxidative stress, and affected mitochondrial function, resulting in apoptosis induction in senescent breast cancer cells. Mito-fisetin-mediated cytotoxicity was due to increased levels of phosphorylated AMPK, decreased levels of AKT and HSP90, and impaired mitophagic response, as judged by the analysis of the markers of mitophagosome formation. Senescent breast cancer cells were found to be more sensitive to mito-fisetin treatment than proliferating ones. We postulate that mitochondrial targeting in the case of fisetin may be considered as a promising anticancer and senotherapeutic strategy to eliminate drug-resistant senescent breast cancer cells.

Survival prediction and analysis of drug-resistance genes in HER2-positive breast cancer

Despite the approval of several therapeutic agents for HER2-positive breast cancer, drug resistance remains a significant challenge, hindering the patient's prognosis. Thus, our study aimed to establish a risk model to predict the prognosis of patients and identify key genes regulating drug resistance in HER2-positive breast cancer. Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), a predictive model was constructed based on 5 drug resistance-related genes, which demonstrated a notable capacity to indicate the survival rates of patients. Besides, through eccDNA and transcriptome sequencing of drug-sensitive and resistant cancer cells, 3 significant DEGs were identified: MED1, MED24, and NMD3. Among them, MED1 showed the most significant elevation in drug-resistance cells, highlighting its crucial role in mediating drug resistance. MED1 may serve as a valuable target for alleviating drug resistance in HER2-positive breast cancer.

Single-Cell RNA-Sequencing: Opening New Horizons for Breast Cancer Research.

Breast cancer is the most prevalent malignant tumor among women with high heterogeneity. Traditional techniques frequently struggle to comprehensively capture the intricacy and variety of cellular states and interactions within breast cancer. As global precision medicine rapidly advances, single-cell RNA sequencing (scRNA-seq) has become a highly effective technique, revolutionizing breast cancer research by offering unprecedented insights into the cellular heterogeneity and complexity of breast cancer. This cutting-edge technology facilitates the analysis of gene expression profiles at the single-cell level, uncovering diverse cell types and states within the tumor microenvironment. By dissecting the cellular composition and transcriptional signatures of breast cancer cells, scRNA-seq provides new perspectives for understanding the mechanisms behind tumor therapy, drug resistance and metastasis in breast cancer. In this review, we summarized the working principle and workflow of scRNA-seq and emphasized the major applications and discoveries of scRNA-seq in breast cancer research, highlighting its impact on our comprehension of breast cancer biology and its potential for guiding personalized treatment strategies.

Safe, simple and multifunctional hydroxyapatite nanoparticles for efficient overcoming of tumor multidrug resistance

Multidrug resistance (MDR) of cancer is the most common obstacle to chemotherapy. Many complex multifunctional nanoparticles have been developed for combination of two or more therapeutics to overcome MDR. Unlike these sophisticated nanoparticles, hydroxyapatite nanoparticles (HAPNs) were found to be able to inhibit cell proliferation of various human cancer cells. Herein, with different MDR cells and chemotherapeutic drugs, we tested whether HAPNs can be widely applied in fighting cancer drug resistance. Rod-shaped HAPNs were synthesized by the aqueous precipitation and then successfully loaded with paclitaxel (PTX) and doxorubicin (DOX) by physical adsorption to obtain pH-responsive drug-loaded nanoparticles, PHAPNs and DHAPNs, respectively. Plain HAPNs exhibited selective cytotoxicity to drug-resistant breast cancer cells MCF-7/ADR, lung cancer cells H69AR and A549/PTX, while spared normal human liver cells L-02. HAPN treatment led to an increase in the apoptosis ratio, a decrease in cell viability and a sustained increase in intracellular calcium ion level in MDR cells. Furthermore, HAPNs facilitated the delivery and accumulation of both drugs, thereby improving the DOX-induced DNA damage in H69AR cells, as well as the acetylation of α-tubulin and cell cycle arrest led by PTX in MCF-7/ADR and A549/PTX cells. Drug-loaded HAPNs greatly enhanced mitochondrial damage, inhibited ATP synthesis and efflux pump activity, and triggered both the intrinsic and extrinsic apoptosis induced by HAPNs or drugs alone. HAPNs acted synergistically with DOX and PTX, resulting in a >6-fold reduction in the IC50 compared with free drugs for these MDR cells. Notably, PHAPNs successfully suppressed the tumor growth in A549/PTX xenograft mice and exhibited excellent biocompatibility in vivo. These findings demonstrated that HAPNs may be widely utilized to reverse the resistance of various drug-resistant cells, providing a simple but practical approach to overcome MDR of cancer.

PAI1 Regulates Cell Morphology and Migration Markers in Trastuzumab-Resistant HER2-Positive Breast Cancer Cells.

HER2-positive breast cancer is a significant cause of mortality. Overcoming trastuzumab resistance requires a deeper understanding of its molecular mechanisms to develop effective therapies. This study investigates the role of plasminogen activator inhibitor-1 (PAI1) in migration and drug resistance in trastuzumab-resistant HER2-positive breast cancer. Trastuzumab resistance poses a significant challenge in clinical management due to its association with aggressive disease behaviour and limited treatment options. This study focuses on PAI1, a key player in the TGF-β signalling pathway, which is implicated in cancer progression and metastasis. Trastuzumab-resistant cell lines (SKBR3 and HCC1954) demonstrated markedly elevated PAI1 expression levels, up to 40-fold compared to parental lines. This elevation was accompanied by increased expression of migration markers such as Col4a1, Fibronectin, ICAM1, Timp2, and Vimentin. Through overexpression and silencing experiments, we observed that modulating PAI1 levels significantly impacts cell morphology, transitioning cells from an epithelial to mesenchymal phenotype. Importantly, combining trastuzumab with aleplasinin, a PAI1 inhibitor, synergistically reduced PAI1 expression in both parental and resistant cell lines. This suggests a potential therapeutic strategy to overcome trastuzumab resistance. These findings emphasise PAI1 as a critical mediator of migration and therapeutic response in HER2-positive breast cancer, offering insights into novel treatment approaches targeting PAI1 to improve clinical outcomes in drug resistance.

The emerging roles of LINC00511 in breast cancer development and therapy.

Breast cancer (BC) is associated with malignant tumors in women worldwide with persistently high incidence and mortality rates. The traditional therapies including surgery, chemotherapy, radiotherapy and targeted therapy have certain therapeutic effects on BC patients, but acquired drug resistance can lead to tumor recurrence and metastasis. This remains a clinical challenge that is difficult to solve during treatment. Therefore, continued research is needed to identify effective targets and treatment methods, to ultimately implement personalized treatment strategies. Several studies have implicated that the long non-coding RNA LINC00511 is closely linked to the occurrence, development and drug resistance of BC. Here we will review the structure and the mechanisms of action of lnc RNA LINC00511 in various cancers, and then explore its expression and its related regulatory mechanisms during BC. In addition, we will discuss the biological functions and the potential clinical applications of LINC00511 in BC.

UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance

UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

SIRT1 promotes doxorubicin-induced breast cancer drug resistance and tumor angiogenesis via regulating GSH-mediated redox homeostasis.

Sirtuin 1 (SIRT1), a member of histone deacetylase III family, plays a pivotal role in mediating chemoresistance in several cancers, including breast cancer. However, the molecular mechanism by which the deregulated SIRT1 promotes doxorubicin (Dox) resistance is still elusive. Here, we showed that the cell proliferation rates and invasive properties of MDA-MB-231 breast cancer cells were increased from low- to high-Dox-resistant cells. In agreement, severe combined immunodeficiency disease (SCID) mice bearing labeled MDA-MB-231high Dox-Res cells showed significantly higher tumor growth, angiogenesis, and metastatic ability than parental MDA-MB-231 cells. Interestingly, the levels of SIRT1 and glutathione (GSH) were positively correlated with the degree of Dox-resistance. Dox-induced SIRT1 promoted NRF2 nuclear translocation with an accompanying increase in the antioxidant response element promotor activity and GSH levels. In contrast, inhibition of SIRT1 by EX527 greatly reversed these events. More so, Dox-resistance-induced pro-proliferative, proangiogenic, and invasive effects were obviated with depletion of either SIRT1 or GSH. Together, Dox-induced SIRT1 promotes dysregulation of redox homeostasis leading to breast cancer chemoresistance, tumor aggressiveness, angiogenesis, and metastasis.

Saikosaponin D potentiates the antineoplastic effects of doxorubicin in drug-resistant breast cancer through perturbing NQO1-mediated intracellular redox balance

BackgroundDrug resistance to doxorubicin (DOX) significantly limits its therapeutic efficacy in breast cancer (BC) patients. Saikosaponin D (SSD), a triterpene saponin derived from the traditional herb Radix Bupleuri, has shown promise as a chemotherapeutic sensitizer in preclinical studies due to its notable antitumor activity. However, the role and mechanism of SSD in DOX-resistant BC cells remain largely unexplored. PurposeThis study aimed to investigate the chemosensitizing effect of SSD on DOX-resistant BC and the underlying molecular mechanisms both in vitro and in vivo. MethodsIn vitro assays, including cell viability, clone formation, three-dimensional tumor spheroid growth, and apoptosis analysis, were conducted to evaluate the synergistic effect of SSD and DOX on resistant BC cells. Reactive oxygen species (ROS), GSH/GSSG, NADPH/NADP+, and NADH/NAD+ detections were employed to assess the impact of SSD on cellular redox homeostasis. Western blotting, cell cycle distribution assay, and DOX uptake assay were performed to further elucidate the possible antineoplastic mechanism of SSD. Finally, a subcutaneous MCF7/DOX cell xenografted model in nude mice was established to identify the in vivo anticarcinogenic effect of SSD combined with DOX. ResultsSSD significantly inhibited cell viability, proliferation, and clone formation, enhancing DOX's anticancer efficacy in vitro and in vivo. Mechanistically, SSD reduced STAT1, NQO1, and PGC-1α protein levels, leading to cellular redox imbalance, excessive ROS generation, and depletion of GSH, NADPH, and NADH. SSD induced DNA damage by disrupting redox homeostasis, resulting in G0/G1 phase cell cycle arrest. Additionally, SSD increased DOX accumulation in BC cells via inhibiting P-gp protein expression and efflux activity. ConclusionWe demonstrated for the first time that SSD enhances the sensitivity of chemoresistant BC cells to DOX by disrupting cellular redox homeostasis through inactivation of the STAT1/NQO1/PGC-1α signaling pathway. This study provides evidence for SSD as an adjuvant agent in drug-resistant BC treatment.

Drug resistance in breast cancer

Objective: The obstacle of resistance throughout breast cancer treatment leads to failure of therapy and progress in the disease. Current developments in our knowledge of the molecular pathways behind resistance to therapies in breast cancer will be covered in this brief review. Materials and methods: The presented data in this review is gathered from multiple sources such as clinical observations (information about how patients react to systemic treatments), experimental models (data gathered from in vitro and in vivo drug resistance simulation framework), review of genetic alterations and epigenetic changes that contribute to resistance is done through genomic and epigenetic studies. The drug resistance mechanisms: target mutations, novel signaling pathways, modifications to the tumor microenvironment, emerging biomarkers, genetic and epigenetic modifications (targeted gene mutations, modifications in drug transporter expression, activation of signaling pathways). Conclusion: Ongoing investigations are essential for identifying successful approaches to combat drug resistance in breast cancer. The process of refinement of combining medicines, development of novel targeted treatments, and research into mechanisms that limit drug transport are among the areas of focus.

Mechanisms of Drug Resistance in Breast Cancer

Breast cancer is a complex disease resulting from the interaction between genetic and environmental factors, and addressing them constitutes one of the major challenges in the treatment of this disease. Resistance to therapies represents a significant obstacle to achieving effective results in the treatment of breast cancer, multiple therapeutic approaches are available to address this disease in patients. The majority of breast cancer cases show estrogen receptor (ERα) expression, and treatments targeting this pathway are critical in their approach. However, the emergence of resistance to these treatments is a common problem, leading to cancer recurrence and relapse. This review provides an overview of the mechanisms contributing to drug resistance, highlighting the relevance of epigenetic factors as promising therapeutic targets to address clinical resistance. Furthermore, it emphasizes the importance of further research to find effective strategies that can overcome this resistance and improve treatment outcomes in patients suffering from breast cancer.

Combination therapy using Cel-CSO/Taxol NPs for reversing drug resistance in breast cancer through inhibiting PI3K/AKT/NF-κB/HIF-1α pathway.

The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.

Research progress in tumor angiogenesis and drug resistance in breast cancer.

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.