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1. Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages

   https://doi.org/10.1016/j.biomaterials.2023.122292  

   Inamdar, Sahil ; Suresh, Abhirami P. ; Mangal, Joslyn L. ; Ng, Nathan D. ; Sundem, Alison ; Behbahani, Hoda Shokrollahzadeh ; Rubino, Thomas E. ; Yaron, Jordan R. ; Khodaei, Taravat ; Green, Matthew ; et al ( October 2023 , Biomaterials)
2. Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment

   https://doi.org/10.1126/sciadv.abm7981  

   Guerrero-Juarez, Christian F. ; Lee, Gun Ho ; Liu, Yingzi ; Wang, Shuxiong ; Karikomi, Matthew ; Sha, Yutong ; Chow, Rachel Y. ; Nguyen, Tuyen T. ; Iglesias, Venus Sosa ; Aasi, Sumaira ; et al ( June 2022 , Science Advances)

   Single-cell analysis of human basal cell carcinoma shows a WNT5A reactive stroma that promotes tumor HSP70 to maintain growth. 

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3. Therapeutic Targeting of Stromal-Tumor HGF-MET Signaling in an Organotypic Triple-Negative Breast Tumor Model

   https://doi.org/10.1158/1541-7786.MCR-21-0317  

   Singh, Sunil ; Lamichhane, Astha ; Rafsanjani Nejad, Pouria ; Heiss, Jacob ; Baumann, Hannah ; Gudneppanavar, Ravindra ; Leipzig, Nic D. ; Konopka, Michael ; Luker, Gary D. ; Tavana, Hossein ( March 2022 , Molecular Cancer Research)

   Abstract The tumor microenvironment (TME) promotes proliferation, drug resistance, and invasiveness of cancer cells. Therapeutic targeting of the TME is an attractive strategy to improve outcomes for patients, particularly in aggressive cancers such as triple-negative breast cancer (TNBC) that have a rich stroma and limited targeted therapies. However, lack of preclinical human tumor models for mechanistic understanding of tumor–stromal interactions has been an impediment to identify effective treatments against the TME. To address this need, we developed a three-dimensional organotypic tumor model to study interactions of patient-derived cancer-associated fibroblasts (CAF) with TNBC cells and explore potential therapy targets. We found that CAFs predominantly secreted hepatocyte growth factor (HGF) and activated MET receptor tyrosine kinase in TNBC cells. This tumor–stromal interaction promoted invasiveness, epithelial-to-mesenchymal transition, and activities of multiple oncogenic pathways in TNBC cells. Importantly, we established that TNBC cells become resistant to monotherapy and demonstrated a design-driven approach to select drug combinations that effectively inhibit prometastatic functions of TNBC cells. Our study also showed that HGF from lung fibroblasts promotes colony formation by TNBC cells, suggesting that blocking HGF-MET signaling potentially could target both primary TNBC tumorigenesis and lung metastasis. Overall, we established the utility of our organotypic tumor model to identify and therapeutically target specific mechanisms of tumor–stromal interactions in TNBC toward the goal of developing targeted therapies against the TME. Implications: Leveraging a state-of-the-art organotypic tumor model, we demonstrated that CAFs-mediated HGF-MET signaling drive tumorigenic activities in TNBC and presents a therapeutic target. 

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4. Tumor penetration of Sub-10 nm nanoparticles: Effect of dendrimer properties on their penetration in multicellular tumor spheroids

   https://doi.org/10.1016/j.nano.2019.102059  

   Bugno, Jason ; Poellmann, Michael J. ; Sokolowski, Karol ; Hsu, Hao-jui ; Kim, Dong-Hwan ; Hong, Seungpyo ( July 2019 , Nanomedicine: Nanotechnology, Biology and Medicine)
5. Reduction of Tumor Growth with RNA-Targeting Treatment of the NAB2–STAT6 Fusion Transcript in Solitary Fibrous Tumor Models

   https://doi.org/10.3390/cancers15123127  

   Li, Yi ; Nguyen, John T. ; Ammanamanchi, Manasvini ; Zhou, Zikun ; Harbut, Elijah F. ; Mondaza-Hernandez, Jose L. ; Meyer, Clark A. ; Moura, David S. ; Martin-Broto, Javier ; Hayenga, Heather N. ; et al ( June 2023 , Cancers)

   Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma. This nonhereditary cancer is the result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12, which fuses the activation domain of STAT6 with the repression domain of NAB2. Currently there is not an approved chemotherapy regimen for SFTs. The best response on available pharmaceuticals is a partial response or stable disease for several months. The purpose of this study is to investigate the potential of RNA-based therapies for the treatment of SFTs. Specifically, in vitro SFT cell models were engineered to harbor the characteristic NAB2–STAT6 fusion using the CRISPR/SpCas9 system. Cell migration as well as multiple cancer-related signaling pathways were increased in the engineered cells as compared to the fusion-absent parent cells. The SFT cell models were then used for evaluating the targeting efficacies of NAB2–STAT6 fusion-specific antisense oligonucleotides (ASOs) and CRISPR/CasRx systems. Our results showed that fusion specific ASO treatments caused a 58% reduction in expression of fusion transcripts and a 22% reduction in cell proliferation after 72 h in vitro. Similarly, the AAV2-mediated CRISPR/CasRx system led to a 59% reduction in fusion transcript expressions in vitro, and a 55% reduction in xenograft growth after 29 days ex vivo. 

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