Divide and Conquer—Targeted Therapy for Triple-Negative Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1396 - 1396

Published: Feb. 7, 2025

Triple-negative breast cancer (TNBC) is the most aggressive and malignant type of with limited treatment options poor prognosis. One significant impediments in TNBC high heterogeneity this disease, as highlighted by detection several molecular subtypes TNBC. Each subtype driven distinct mutations pathway aberrations, giving rise to specific characteristics closely connected clinical behavior, outcomes, drug sensitivity. This review summarizes knowledge regarding how it can be harnessed devise tailored strategies instead blindly using targeted drugs. We provide an overview novel agents key insights about new modalities emphasis on androgen receptor signaling pathway, stem cell-associated pathways, phosphatidylinositol 3-kinase (PI3K)/AKT growth factor signaling, immunotherapy.

Language: Английский

---

The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4335 - 4357

Published: March 1, 2025

Monoclonal antibodies (mAbs) have transformed cancer treatment by providing highly targeted and effective therapies that specifically attack cells, thus reducing the likelihood of adverse events (AEs) in patients. mAbs exert their action through various mechanisms, such as receptor blockade, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent (CDC), inhibition immune checkpoints (eg, PD-1, PD-L1, CTLA-4). These led to significant improvements several cancers, including HER2-positive breast cancer, non-small cell lung (NSCLC), melanoma. The efficacy mAb therapy is influenced intrinsic extrinsic factors, environmental exposures, psychosocial infection status, ways life, tumor microenvironment (TME), all which can impact responses outcomes. Notably, therapeutic benefits are often accompanied immune-related AEs (irAEs), vary from mild severe affect multiple organ systems. dual nature mAbs-stimulating antitumor while also inducing side effects-presents a notable challenge clinical practice. This review highlights importance proactive strategies for managing irAEs, early detection, corticosteroid use, immunosuppressive treatments, urgent need reliable predictive biomarkers improve Advancements prevention, prediction, management irAEs essential enhance safety effectiveness mAb-based therapies, ultimately aiming patient

Language: Английский

---

Potential role of CFLAR in enhancing 5-FU sensitivity and modulating immune cell infiltration in breast cancer

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 10, 2025

Breast cancer (BRCA), the most common malignancy among women, is a highly heterogeneous disease. Chemoresistance major factor leading to treatment failure in BRCA. However, mechanisms underlying development of chemoresistance remain unclear. In this study, we performed comprehensive bioinformatic analysis examine role cell death-associated genes BRCA treatment. Specifically, focused on caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR), which was identified as co-differentially expressed molecule potential prognostic values. We then validated these findings through vitro experiments BT- 549 MDA-MB- 231 breast cells. Based bioinformatics analysis, CFLAR expression found be downregulated patients BRCA, whereas its high significantly associated improved prognosis. Kyoto Encyclopedia Genes Genomes (KEGG) pathway indicated that aberrantly potentially oxidative phosphorylation, T receptor signaling, NADH dehydrogenase (ubiquinone) activity. demonstrated overexpression inhibited generation reactive oxygen species (ROS), consequently promoting 5-fluorouracil (5-FU) sensitivity The positively correlated abundance several tumor-infiltrating immune cells, especially CD8 + further supporting regulation. conclusion, study reveals novel roles enhancing chemotherapy patient outcome underscores therapeutic target. These results supported target biomarker patients.

Language: Английский

---

Prognostic impact of metformin in solid cancer patients receiving immune checkpoint inhibitors: novel evidences from a multicenter retrospective study

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

Objective: Metformin as a common antidiabetic drug, has recently found to exert its anti-cancer and immunomodulatory effect in numerous preclinical studies. This study aims clarify the prognostic impact of metformin use solid cancer patients receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective cohort enrolling 516 who received ICI-based therapy between 2018 2023 at three hospitals was analyzed. The primary endpoints included overall survival (OS) progression-free (PFS). In addition, bioinformatics analysis based on TCGA GSE performed investigate significance target genes (MTGs) their correlation with infiltration non-small cell lung (NSCLC) patients. Results: entire cohort, total 76 before and/or during ICI therapy. global demonstrated that unrelated OS ( p = 0.064) PFS 0.059) ICI-treated patients, which confirmed subgroups esophagus, hepatobiliary or pancreatic (all > 0.05). However, significantly correlated better 0.012) 0.005) also identified an independent favorable factor for these five MTGs (RPS6KA5, RORA, SH3BP5, NUPR1, CD40LG) NSCLC all downregulated tissues compared normal tissues. expressions not only could effectively stratify but cells such CD4 + CD8 T cells. Conclusion: potential serve novel clinical biomarkers druggable targets immunotherapy. Considering limitations, actual needs be clarified by more trials.

Language: Английский

---