Advancing Breast Cancer Treatment: The Role of Immunotherapy and Cancer Vaccines in Overcoming Therapeutic Challenges DOI Creative Commons
Marco Palma

Vaccines, Год журнала: 2025, Номер 13(4), С. 344 - 344

Опубликована: Март 24, 2025

Breast cancer (BC) remains a significant global health challenge due to its complex biology, which complicates both diagnosis and treatment. Immunotherapy vaccines have emerged as promising alternatives, harnessing the body’s immune system precisely target eliminate cells. However, several key factors influence selection effectiveness of these therapies, including BC subtype, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), PD-L1 expression, HER2 resistance, microenvironment (TME). subtypes play critical role in shaping treatment responses. Triple-negative breast (TNBC) exhibits highest sensitivity immunotherapy, while HER2-positive hormone receptor-positive (HR+) often require combination strategies for optimal outcomes. High TMB enhances responses by generating neoantigens, making tumors more susceptible checkpoint inhibitors (ICIs); whereas, low may indicate resistance. Similarly, elevated TIL levels are associated with better immunotherapy efficacy, expression serves predictor inhibitor success. Meanwhile, resistance an immunosuppressive TME contribute evasion, highlighting need multi-faceted approaches. Current immunotherapies encompass range targeted treatments. HER2-directed such trastuzumab pertuzumab, block dimerization enhance antibody-dependent cellular cytotoxicity (ADCC), small-molecule inhibitors, like lapatinib tucatinib, suppress signaling curb growth. Antibody–drug conjugates (ADCs) improve targeting coupling monoclonal antibodies cytotoxic agents, minimizing off-target effects. ICIs, pembrolizumab, restore T-cell function, CAR-macrophage (CAR-M) therapy leverages macrophages reshape overcome While particularly TNBC, has demonstrated promise eliciting durable responses, efficacy varies across subtypes. Challenges immune-related adverse events, mechanisms, high costs, delayed remain barriers widespread vaccines—including protein-based, whole-cell, mRNA, dendritic cell, epitope-based vaccines—aim stimulate tumor-specific immunity. Though clinical success been limited, ongoing research is refining vaccine formulations, integrating identifying biomarkers improved patient stratification. Future advancements will depend on optimizing through biomarker-driven approaches, addressing heterogeneity, developing innovative therapies By leveraging strategies, researchers aim ultimately

Язык: Английский

Druggable Molecular Networks in BRCA1/BRCA2-Mutated Breast Cancer DOI Creative Commons
Federica Carbone, Pietro Ancona, Stefano Volinia

и другие.

Biology, Год журнала: 2025, Номер 14(3), С. 253 - 253

Опубликована: Март 2, 2025

Mutations in the tumor suppressor genes BRCA1 and BRCA2 are associated with triple-negative breast cancer phenotype, particularly aggressive hard-to-treat tumors lacking estrogen, progesterone, human epidermal growth factor receptor 2. This research aimed to understand metabolic genetic links behind mutations investigate their relationship effective therapies. Using Cytoscape software, two networks were generated through a bibliographic analysis of articles retrieved from PubMed-NCBI database. We identified 98 deregulated by BRCA mutations, 24 modulated In particular, BIRC5, SIRT1, MYC, EZH2, CSN2 influenced BRCA1, while BCL2, BAX, BRIP1 mutation. Moreover, study evaluated efficacy several promising therapies, targeting only BRCA1/BRCA2-mutated cells. this context, CDDO-Imidazolide was shown increase ROS levels induce DNA damage. Similarly, resveratrol decreased expression anti-apoptotic gene BIRC5 it increased SIRT1 both vitro vivo. Other specific drugs found apoptosis selectively BRCA-mutated cells or block cell when mutation occurs, i.e., 3-deazaneplanocin A, genistein daidzein, PARP inhibitors. Finally, over-representation on highlights ferroptosis proteoglycan pathways as potential drug targets for more treatments.

Язык: Английский

Процитировано

0
BUB1 Inhibition Induces Ferroptosis in Triple-Negative Breast Cancer Cell Lines DOI Creative Commons

Sushmitha Sriramulu,

Shivani Thoidingjam,

Stephen L. Brown

и другие.

DNA, Год журнала: 2025, Номер 5(1), С. 16 - 16

Опубликована: Март 12, 2025

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited effective treatments available, including targeted therapies, often leading to poor prognosis. Mitotic checkpoint kinase BUB1 frequently overexpressed in TNBC and correlates survival outcomes suggesting its potential as therapeutic target. This study explores the cytotoxicity of cells inhibition, alone or combination radiation demonstrates that ferroptosis, an iron-dependent form programmed cell death, has role. Methods: lines (SUM159, MDA-MB-231, BT-549) were treated inhibitor BAY1816032 (BUB1i) ferroptosis activator RSL3 without 4 Gy irradiation. Cell viability assays conducted assess treatment effects, qPCR analyses measured expression key markers ACSL4, GPX4, PTGS2, SLC7A11, NCOA4, IREB2, NFS1, TFRC expression, TBARS assay lipid peroxidation levels. Ferroptosis specificity was confirmed through co-treatment Ferrostatin-1 (F-1). Results: In all studied, inhibition significantly induced marked by increased ACSL4 decreased GPX4 The BUB1i further amplified these ferroptotic markers, at least additive effect, which not present radiation. Co-treatment reversed BUB1i-mediated death may involve signaling lines. Conclusions: independently induce lines, enhanced when combined activator. Further research warranted delineate molecular mechanism BUB1-mediated TNBC.

Язык: Английский

Процитировано

0
Advancing Breast Cancer Treatment: The Role of Immunotherapy and Cancer Vaccines in Overcoming Therapeutic Challenges DOI Creative Commons
Marco Palma

Vaccines, Год журнала: 2025, Номер 13(4), С. 344 - 344

Опубликована: Март 24, 2025

Breast cancer (BC) remains a significant global health challenge due to its complex biology, which complicates both diagnosis and treatment. Immunotherapy vaccines have emerged as promising alternatives, harnessing the body’s immune system precisely target eliminate cells. However, several key factors influence selection effectiveness of these therapies, including BC subtype, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), PD-L1 expression, HER2 resistance, microenvironment (TME). subtypes play critical role in shaping treatment responses. Triple-negative breast (TNBC) exhibits highest sensitivity immunotherapy, while HER2-positive hormone receptor-positive (HR+) often require combination strategies for optimal outcomes. High TMB enhances responses by generating neoantigens, making tumors more susceptible checkpoint inhibitors (ICIs); whereas, low may indicate resistance. Similarly, elevated TIL levels are associated with better immunotherapy efficacy, expression serves predictor inhibitor success. Meanwhile, resistance an immunosuppressive TME contribute evasion, highlighting need multi-faceted approaches. Current immunotherapies encompass range targeted treatments. HER2-directed such trastuzumab pertuzumab, block dimerization enhance antibody-dependent cellular cytotoxicity (ADCC), small-molecule inhibitors, like lapatinib tucatinib, suppress signaling curb growth. Antibody–drug conjugates (ADCs) improve targeting coupling monoclonal antibodies cytotoxic agents, minimizing off-target effects. ICIs, pembrolizumab, restore T-cell function, CAR-macrophage (CAR-M) therapy leverages macrophages reshape overcome While particularly TNBC, has demonstrated promise eliciting durable responses, efficacy varies across subtypes. Challenges immune-related adverse events, mechanisms, high costs, delayed remain barriers widespread vaccines—including protein-based, whole-cell, mRNA, dendritic cell, epitope-based vaccines—aim stimulate tumor-specific immunity. Though clinical success been limited, ongoing research is refining vaccine formulations, integrating identifying biomarkers improved patient stratification. Future advancements will depend on optimizing through biomarker-driven approaches, addressing heterogeneity, developing innovative therapies By leveraging strategies, researchers aim ultimately

Язык: Английский

Процитировано

0