ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Controlled extracellular matrix degradation in breast cancer tumors improves therapy by trastuzumab.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 70 citations in OpenAlex.
- Role of Relaxin Signaling in Cancer: A Review.Biochemical pharmacology · 2024Review
- CAF-induced physical constraints controlling T cell state and localization in solid tumours.Nature reviews. Cancer · 2024Review
- Car T Cells in Solid Tumors: Overcoming Obstacles.International journal of molecular sciences · 2024Review
- Noninvasive identification of HER2-low-positive status by MRI-based deep learning radiomics predicts the disease-free survival of patients with breast cancer.European radiology · 2024Article
- The diverse influences of relaxin-like peptide family on tumor progression: Potential opportunities and emerging challenges.Heliyon · 2024Review
- Elastin-like Recombinamer Hydrogels as Platforms for Breast Cancer Modeling.Biomacromolecules · 2023Article
- Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?Frontiers in immunology · 2022Review
- CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil.Frontiers in immunology · 2022Review
- Delivery of therapeutic oligonucleotides in nanoscale.Bioactive materials · 2022Review
- Strategies to enhance monoclonal antibody uptake and distribution in solid tumors.Cancer biology & medicine · 2021Review
- Transient Competitive Inhibition Bypasses the Binding Site Barrier to Improve Tumor Penetration of Trastuzumab and Enhance T-DM1 Efficacy.Cancer research · 2021Article
- The In Vivo Selection Method in Breast Cancer Metastasis.International journal of molecular sciences · 2021Review
- Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Improved ADM Penetration Distance and Therapeutic Efficiency in a Rabbit VX2 Liver Cancer Model by Relaxin Infusion Combined with Transcatheter Chemoembolization Through Hepatic Artery.Cancer management and research · 2020Article
- Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer.Breast cancer research : BCR · 2019Article
- Localized co-delivery of collagenase and trastuzumab by thermosensitive hydrogels for enhanced antitumor efficacy in human breast xenograft.Drug delivery · 2018Article
- Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.Journal of hematology & oncology · 2018Review
- Three-dimensional tumor cell cultures employed in virotherapy research.Oncolytic virotherapy · 2018Review
- Robust method for identification of prognostic gene signatures from gene expression profiles.Scientific reports · 2017Article
- Targeting Androgen Receptor in Treating HER2 Positive Breast Cancer.Scientific reports · 2017Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Extracellular matrix (ECM) in solid tumors affects the effectiveness of therapeutics through blocking of intratumoral diffusion and/or physical masking of target receptors on malignant cells. In immunohistochemical studies of tumor sections from breast cancer patients and xenografts, we observed colocalization of ECM proteins and Her2/neu, a tumor-associated antigen that is the target for the widely used monoclonal antibody trastuzumab (Herceptin). We tested whether intratumoral expression of the peptide hormone relaxin (Rlx) would result in ECM degradation and the improvement of trastuzumab therapy. As viral gene delivery into epithelial tumors with extensive tumor ECM is inefficient, we used a hematopoietic stem cell (HSC)-based approach to deliver the Rlx gene to the tumor. In mouse models with syngeneic breast cancer tumors, HSC-mediated intratumoral Rlx expression resulted in a decrease of ECM proteins and enabled control of tumor growth. Moreover, in a model with Her2/neu-positive BT474-M1 tumors and more treatment-refractory tumors derived from HCC1954 cells, we observed a significant delay of tumor growth when trastuzumab therapy was combined with Rlx expression. Our results have implications for antibody therapy of cancer as well as for other anticancer treatment approaches that are based on T-cells or encapsulated chemotherapy drugs.
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