Breast Cancer Treatment Strategies Targeting the Tumor Microenvironment: How to Convert “Cold” Tumors to “Hot” Tumors

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7208 - 7208

Опубликована: Июнь 29, 2024

Breast cancer characterized as "cold tumors" exhibit low levels of immune cell infiltration, which limits the efficacy conventional immunotherapy. Recent studies have focused on strategies using nanotechnology combined with tumor microenvironment modulation to transform into "hot tumors". This approach involves use functionalized nanoparticles that target and modify promote infiltration activation antitumor cells. By delivering activators or blocking immunosuppressive signals, these activate otherwise dormant responses, enhancing immunogenicity therapeutic response. These not only promise increase response rate breast patients existing immunotherapies but also may pave new avenues, providing a direction for immunotherapy cancer.

Язык: Английский

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Signaling pathway dysregulation in breast cancer

Oncotarget, Год журнала: 2025, Номер 16(1), С. 168 - 201

Опубликована: Март 13, 2025

// Dinara Ryspayeva 1 , 2 3 4 Attila A. Seyhan 5 William J. MacDonald Connor Purcell Tyler Roady Maryam Ghandali Nataliia Verovkina Wafik S. El-Deiry 7 Martin Taylor 6 and Stephanie L. Graff Laboratory of Translational Oncology Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, RI 02903, USA Department Pathology Medicine, Joint Program in Biology, Lifespan Health System Legorreta Center at Pathobiology Graduate Program, on the Biology Aging, Hematology/Oncology Division, Correspondence to: Ryspayeva, email: [email protected] Keywords: breast cancer; oncogenic pathways; signal dysregulation therapeutic approaches; clinical trials Received: December 20, 2024 Accepted: March 03, 2025 Published: 13, Copyright: © et al. This is an open access article distributed under terms Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, reproduction any medium, provided original author source are credited. ABSTRACT provides a comprehensive analysis signaling pathways implicated cancer (BC), most prevalent malignancy among women leading cause cancer-related mortality globally. Special emphasis placed structural dynamics protein complexes that integral to regulation these cascades. Dysregulation cellular fundamental aspect BC pathophysiology, with both upstream downstream cascade activation contributing process aberrations not only drive tumor growth, but also contribute resistance against current treatments. The review explores alterations within across different subtypes highlights potential strategies targeting pathways. Additionally, influence specific mutations decision-making examined, underscoring their relevance particular subtypes. discusses approved modalities ongoing disrupted However, further investigation necessary fully elucidate underlying mechanisms optimize personalized treatment approaches.

Язык: Английский

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Advances in cancer immunotherapy: historical perspectives, current developments, and future directions

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Май 7, 2025

Cancer immunotherapy, encompassing both experimental and standard-of-care therapies, has emerged as a promising approach to harnessing the immune system for tumor suppression. Experimental strategies, including novel immunotherapies preclinical models, are actively being explored, while established treatments, such checkpoint inhibitors (ICIs), widely implemented in clinical settings. This comprehensive review examines historical evolution, underlying mechanisms, diverse strategies of cancer highlighting its applications ongoing advancements. The delves into essential components anticancer immunity, dendritic cell activation, T priming, surveillance, addressing challenges posed by evasion mechanisms. Key immunotherapeutic vaccines, oncolytic viruses, adoptive transfer, ICIs, discussed detail. Additionally, role nanotechnology, cytokines, chemokines, adjuvants enhancing precision efficacy were explored. Combination particularly those integrating immunotherapy with radiotherapy or chemotherapy, exhibit synergistic potential but necessitate careful management reduce side effects. Emerging factors influencing outcomes, heterogeneity, gut microbiota composition, genomic epigenetic modifications, also examined. Furthermore, molecular mechanisms therapeutic resistance analyzed, focus on contributions noncoding RNAs alterations, along innovative intervention strategies. emphasizes recent advancements, particular attention biomarker-driven approaches aimed at optimizing patient prognosis. Challenges immunotherapy-related toxicity, limited solid tumors, production constraints highlighted critical areas future research. Advancements personalized therapies delivery systems proposed avenues enhance treatment effectiveness accessibility. By incorporating insights from multiple disciplines, this aims deepen understanding application ultimately fostering more effective accessible solutions.

Язык: Английский

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Immunocytes interact directly with cancer cells in the tumor microenvironment: one coin with two sides and future perspectives

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 22, 2024

The tumor microenvironment is closely linked to the initiation, promotion, and progression of solid tumors. Among its constitutions, immunologic cells emerge as critical players, facilitating immune evasion progression. Apart from their indirect impact on anti-tumor immunity, immunocytes directly influence neoplastic cells, either bolstering or impeding advancement. However, current therapeutic modalities aimed at alleviating immunosuppression regulatory effector cell populations may not consistently yield satisfactory results in various tumors, such breast carcinoma, colorectal cancer, etc. Therefore, this review outlines summarizes direct, dualistic effects T innate lymphoid B eosinophils, tumor-associated macrophages within microenvironment. also delves into underlying mechanisms involved presents outcomes clinical trials based these direct effects, aiming propose innovative efficacious strategies for addressing

Язык: Английский

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Targeting “don’t eat me” signal: breast cancer immunotherapy

Breast Cancer Research and Treatment, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Язык: Английский

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The multiple functions and mechanisms of long non-coding RNAs in regulating breast cancer progression

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Breast cancer (BC) is a malignant tumor that has the highest morbidity and mortality rates in female population, its high tendency to metastasize main cause of poor clinical prognosis. Long non-coding RNAs (lncRNAs) have been extensively documented exhibit aberrant expression various cancers influence progression via multiple molecular pathways. These lncRNAs not only modulate numerous aspects gene cells, such as transcription, translation, post-translational modifications, but also play crucial role reprogramming energy metabolism by regulating metabolic regulators, which particularly significant advanced BC. This review examines characteristics mechanisms BC both intracellularly (e.g., cell cycle, autophagy) extracellularly microenvironment). Furthermore, we explore potential specific their regulatory factors markers therapeutic targets. Lastly, summarize application treatment BC, aiming offer novel personalized options for patients.

Язык: Английский

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CD47 Contributes to the Proliferation of Breast Cancer

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(3)

Опубликована: Март 5, 2025

Background: The CD47 molecule (CD47) performs a novel role in regulating immunoreactions by binding to signal-regulatory protein alpha (SIRPα), resulting the tumorigenesis of multiple malignant neoplasms. However, its effects and mechanisms breast cancer (BC) remain unknown. Methods: To explore molecular explicit impacts CD47, we screened two databases for CD47-associated signaling pathways cellular functions. BC samples patients’ basic information were collected identify statistical significance expression. We also constructed experiments validate regulatory cell proliferation. Results: Analysis TCGA-BRCA, GSE42568, GSE15852 datasets demonstrated an elevated level tissues. A Venn diagram revealed 11,194 co-expressed genes, pathway analysis linked levels critical pathways, such as cytokine-receptor interactions Janus kinase/signal transducer activator transcription (JAK/STAT) signaling, which are integral proliferation invasiveness. Clinical data from 108 specimens showed that localization was primarily membranous, with higher correlating marker Ki-67 (Ki-67) expression (p < 0.0001) advanced tumor/node/metastasis (TNM) stage 0.0001). Additionally, functional assays depletion reduced viability 0.01), migration 0.001), invasion 0.05 4T1 cells; p 0.001 MDA-MB-231 cells) vitro led smaller tumor volumes vivo. Conclusion: is key regulator invasiveness serves potential assessing aggressiveness guiding therapeutic strategies.

Язык: Английский

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Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies

International Journal of Biological Sciences, Год журнала: 2025, Номер 21(6), С. 2606 - 2628

Опубликована: Март 24, 2025

Natural killer (NK) cells have emerged as a novel and effective treatment for breast cancer. Nevertheless, the cancer tumor microenvironment (TME) manifests multiple immunosuppressive mechanisms, impeding proper execution of NK cell functions. This review summarizes recent research on influence TME functionality in It delves into effects internal environment elucidates roles diverse stromal components, immune cells, signaling molecules regulating activity within TME. also therapeutic strategies based small-molecule inhibitors, antibody therapies, natural products, well progress preclinical clinical trials. By enhancing our understanding formulating to counteract its effects, we could fully harness promise treatment.

Язык: Английский

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High Expression of Complement 3 Enhances the Efficacy of Neoadjuvant Chemotherapy Prior to Oncoplastic Surgery for HER2-Positive Breast Cancer

Cancer Biotherapy and Radiopharmaceuticals, Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Background: Neoadjuvant chemotherapy for breast cancer (BC) improves patient prognosis, but its efficacy is hindered by the disease's high heterogeneity. This study enhances effectiveness of targeted therapy to improve clinical outcomes. Methods: enrolled 335 patients from three centers. Differentially expressed genes were identified using DESeq2, and Venn analysis was applied identify hub Complement genes. Hub gene expression validated through public databases IHC in real-world samples. In addition, associations between these factors evaluated. Survival analysis, log-rank test, assessed overall survival (OS), disease-specific (DSS), progression-free interval (PFI) as end points. The authors also locate 3 position immunofluorescence. Results: C3 a associated with trastuzumab sensitivity. shows higher normal than tumor tissues. highly HER2-negative early-stage BC, showed no differences lymph node or metastasis subgroups. High correlated better OS, DSS, PFI, particularly HER2+ patients. confirmed tissues lowest triple-negative BC. Immunofluorescence findings suggest that recruits complement receptor 2 enhance Conclusions: finding highlights potential therapeutic outcomes pave way more personalized treatment strategies

Язык: Английский

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Successful targeting of multidrug-resistant tumors with bispecific antibodies

mAbs, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 18, 2025

Multidrug resistance (MDR) hinders efficacious cancer chemotherapy. Overexpression of the P-glycoprotein (P-gp) efflux pump (EP) on cells is a primary cause MDR since it expels numerous anticancer drugs. Small molecule intracellular P-gp antagonists have been investigated clinically to redress but failed primarily due adverse effects in normal tissue. We used new approach counteract with bispecific antibodies (BsAbs) that simultaneously bound and CD47 cis not Affinities individual arms BsAbs were low enough minimize tissue binding, but, when two targets co-located cells, both BsAb engaged effective avidity. Proof-of-concept was shown three different xenograft tumor models non-humanized chimeric (targeting CD47) potently restored sensitivity paclitaxel. Fully humanized variants successfully developed characterized. Significant anti-tumor efficacy observed combined paclitaxel as single agents absence Treatment cancers using this novel has several distinct advantages over prior efforts small antagonists, including 1) invoking direct immune attack tumors, 2) multimodal mechanisms action, 3) tumor-specific targeting (with reduced toxicity tissue), 4) broad applicability compatibility other therapeutics.

Язык: Английский

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