Triple Negative Breast Cancer

P2, N=146, Active, not recruiting, Queen Mary University of London | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Jan 2021 --> Aug 2026

P=N/A, N=60, Recruiting, Kliniken Essen-Mitte | Not yet recruiting --> Recruiting

This EV membrane topology-based mechanism operates independently of canonical EV cargo internalization. Neutralizing EVs-TSPAN8+ with a monoclonal antibody synergized with anti-PD-1 therapy in preclinical models, suggesting a potential approach targeting both CSCs and TME immunosuppression, particularly in TNBC subpopulation with high TSPAN8+ CSCs.

Our findings demonstrated that ginsenoside Rg3 regulates PD-L1 stability by downregulating its glycosylation, thereby improving atezolizumab efficacy to exert the anti-tumor immune therapy.

Our approach combining bio-computing as well as experimental validation allows to propose a gene signature, the high expression of which predicts TNBC patient survival. Down modulation of these genes could be promising against TNBCs.

This dual-hit mechanism exhausts the aspartate pool and restricts nucleotide biosynthesis, thereby selectively suppressing BrM outgrowth. Our findings uncover a therapeutic strategy for TNBC BrMs.

In addition, we highlight the importance of molecular stratification and biomarker-driven approaches to identify patients most likely to benefit from anti-angiogenic therapy. Overall, while VEGFR-targeted therapy alone has shown limited success, rational combination strategies and improved patient selection may significantly enhance its clinical utility in TNBC.

In vivo studies using xenograft models established with MDA-MB-231 cells stably expressing miR-99b-5p knockdown showed marked tumor regression, further supporting its oncogenic role. Collectively, these findings establish miR-99b-5p as a context-specific oncogenic miRNA in breast cancer and a promising therapeutic target, particularly for TNBC, where targeted treatment options remain limited.

These findings identify PPP as a conserved regulatory layer modulating YAP-driven oncogenic transcription. Loss of NELFA may enhance oncogenic transcriptional programs specifically in TNBC, highlighting its potential relevance as a context-dependent biomarker in aggressive breast cancer subtypes.

Concurrently, dysregulated signaling, such as the Wnt/β-catenin pathway, inhibits dendritic cell maturation and recruits Myeloid-Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs) into the tumor microenvironment, thereby blunting the anti-tumor T cell response. This review examines the role of key pluripotency regulators in TNBC-mediated immune evasion, highlighting emerging immunotherapeutic strategies targeting these networks and summarizing current clinical research.

Future directions emphasize next-generation ICIs, optimized combination regimens, and AI-driven biomarker integration to achieve durable, personalized treatments. This review underscores the potential of immunotherapy to redefine TNBC management while highlighting the imperative for continued innovation to address unmet clinical needs.

ST3GAL4-driven glycosphingolipid metabolism promotes tumor immune evasion and aggressiveness in TNBC. This metabolic-immune coupling axis represents a potential therapeutic target, offering mechanistic rationale for combining metabolic and immune checkpoint blockade strategies.