ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
A Self-Assembling LYTAC Mediates CTGF Degradation and Remodels Inflammatory Tumor Microenvironment for Triple-Negative Breast Cancer Therapy.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Lysosome-directed targeted protein degradation technologies for overcoming cancer drug resistance: mechanisms, design principles, and therapeutic opportunities.Drug delivery · 2026Review
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- AI-Designed TREM1-Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RIBOTAC-mediated degradation of hsa-microRNA-301a-3p suppresses TNBC bone metastasis.Science advances · 2026Article
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Dynamic reprogramming of the tumor immune network via multicycle checkpoint degradation for cancer immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TPDdb: the comprehensive database of targeted protein degrader.Nucleic acids research · 2026Article
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Targeting CTGF overcomes resistance to CSF1R inhibitors by preventing CAF activation in colorectal cancer.Cell reports. Medicine · 2025Article
- A Self-Assembling LYTAC Mediates CTGF Degradation and Remodels Inflammatory Tumor Microenvironment for Triple-Negative Breast Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
As a multifunctional extracellular protein, connective tissue growth factor (CTGF/CCN2) is significantly associated with the progression and prognosis of triple-negative breast cancer (TNBC). However, current blockade therapies targeting CTGF's multiple domains are limited, creating substantial challenges in treatment. Lysosome-targeting chimeras (LYTACs) have emerged as a promising approach for achieving complete protein degradation and inhibiting CTGF's various bioactivities. In this study, a self-assembling LYTAC nanoplatform, NanoCLY, designed to tumor microenvironment (TME)-responsively degrade CTGF is presented. The complete degradation of CTGF downregulates the TGF-β signaling pathway and disrupts the CTGF-IL-6 cell crosstalk within the TME, which further inhibits the activation of inflammatory cancer-associated fibroblasts (CAFs) and alleviates the inflammatory TME. Notably, the anti-TNBC effect of LYTAC-based CTGF degradation therapy surpasses that of antibody-based blockade therapy in both in vitro and in vivo models. The findings provide a proof of concept for CTGF degradation in TNBC and introduce the first CTGF-LYTAC nanoplatform aimed at TME-directed therapy.
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