Review
Engineering, Biomedical
Zhenzhen Zhou, Jianyu He, Yuan Pang, Wei Sun
Summary: Recent advances in tumor microenvironment (TME) modeling and its applications to cancer therapy have led to dramatic changes in the management of multiple malignancies. Various three-dimensional (3D) cell culture techniques have been developed to understand and replicate cancer biology. This review highlights the progress in in vitro 3D TME modeling techniques, such as cell-based, matrix-based, and vessel-based approaches, and their applications in studying tumor-stroma interactions and responses to cancer therapies. The review also addresses the limitations of current TME modeling approaches and proposes new ideas for constructing more clinically relevant models.
Review
Biochemistry & Molecular Biology
Louise Orcheston-Findlay, Samuel Bax, Robert Utama, Martin Engel, Dinisha Govender, Geraldine O'Neill
Summary: The life expectancy of patients with high-grade glioma (HGG) has not improved, highlighting the need for advanced models for future improvement. Currently, advanced models are crucial for identifying new targets and evaluating treatment modalities. While pediatric HGG (pHGG) models lag behind those of adults, there is hope to bring this to light and improve pGBM models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Peiyuan Mu, Shujuan Zhou, Tao Lv, Fan Xia, Lijun Shen, Juefeng Wan, Yaqi Wang, Hui Zhang, Sanjun Cai, Junjie Peng, Guoqiang Hua, Zhen Zhang
Summary: Immunotherapy is a rapidly developing therapeutic approach that has revolutionized cancer treatment and revitalized tumor immunology research. 3D in vitro models, which can maintain tumor cells in a near-native state, are emerging as powerful tools and have been widely applied in oncology research. The novel 3D culture methods, such as co-culture of organoids and immune cells, ALI culture, 3D-microfluidic culture, and 3D-bioprinting, offer new approaches for tumor immunology study and have applications in personalized treatment, immunotherapy optimization, and adoptive cell therapy. This review introduces commonly used 3D in vitro models and summarizes their applications in different aspects of tumor immunology research. A preliminary analysis of the current shortcomings of these models and the outlook of future development is also provided.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Immunology
Cai-Ping Sun, Huan-Rong Lan, Xing-Liang Fang, Xiao-Yun Yang, Ke-Tao Jin
Summary: Cancer immunotherapy modulates the immune system to treat diseases, but conventional animal and in vitro models fail to accurately simulate the tumor immune microenvironment. More physiomimetic cancer models, such as patient-derived organoids, are needed to evaluate the efficacy of immunotherapy agents. The dynamic interactions between neoplastic cells and non-neoplastic host components in the tumor immune microenvironment play a crucial role in carcinogenesis, tumor metastasis, cancer progression, and drug resistance. Tumor organoids can effectively recapitulate the tumor immune microenvironment and be used for testing immunotherapy agents and personalized cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Teresa Ho, Rasha Msallam
Summary: Understanding the mechanisms of tumor immunosuppression is crucial for improving cancer immunotherapy. The rapid development of 3D organoid model systems provides a new approach for studying tumor immunosuppression. Developing patient-specific models is essential for investigating personalized immunotherapy.
Review
Biochemistry & Molecular Biology
Irena Wieleba, Kamila Wojas-Krawczyk, Pawel Krawczyk, Janusz Milanowski
Summary: Despite significant progress in modern therapies, lung cancer remains a leading cause of death. Proper planning of preclinical research using 3D tumor microenvironment in vitro models is crucial for developing new anti-cancer drugs. The challenge lies in choosing the best tool for studying tumor microenvironments, especially in diverse lung cancer cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Li-Feng Hu, Xue Yang, Huan-Rong Lan, Xing-Liang Fang, Xiao-Yi Chen, Ke-Tao Jin
Summary: Personalized cancer medicine involves specific treatment for each patient, as the heterogeneous tumor microenvironment and individual differences can significantly impact therapy response and clinical outcomes. Current in vitro and in vivo models inadequately replicate the native tumor microenvironment, highlighting the need for native tumor microenvironment mimicking models. The development of 3D culture models has allowed for better evaluation of chemoresistance and drug functionality in the presence of cell-cell interactions, such as patient-derived tumor xenografts and organoid cultures.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Engineering, Biomedical
Pei Zhuang, Yi-Hua Chiang, Maria Serafim Fernanda, Mei He
Summary: Although cancer remains a leading cause of mortality worldwide, efforts in anticancer therapeutics are hindered by the lack of robust prediction models. Multicellular tumor spheroids, a popular three-dimensional culture model for avascular tumors, have limitations in controlling cellular and structural organization. 3D bioprinting, with its spatial control, scalability, and reproducibility, holds promise for generating more faithful tumor models and advancing our understanding of tumor progression.
INTERNATIONAL JOURNAL OF BIOPRINTING
(2021)
Review
Pharmacology & Pharmacy
Rachel Ringquist, Delta Ghoshal, Ritika Jain, Krishnendu Roy
Summary: The tumor microenvironment (TME) is shaped by dynamic interactions between various cell types, influencing immune responses and therapeutic resistance. Efforts are being made to understand key components and model complexity for studying immunotherapies. Challenges in sourcing and quality control of TME cells persist in developing reproducible platforms for cell therapies.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Poonam Trivedi, Rui Liu, Hongjie Bi, Chunlin Xu, Jessica M. Rosenholm, Malin Akerfelt
Summary: Current statistics show that 90% of all human cancers originate from epithelial cells, with breast and prostate cancer being common examples. However, many preclinically approved drugs fail in clinical trials due to issues such as oversimplified in vitro models and a lack of mimicry of the tumor microenvironment. Thus, researchers are focusing on developing experimental models, including 2D and 3D cell cultures, and animal models to better understand and treat epithelial cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Luc Magre, Monique M. A. Verstegen, Sonja Buschow, Luc J. W. van der Laan, Maikel Peppelenbosch, Jyaysi Desai
Summary: In the past decade, immune system-based treatments have greatly advanced the field of cancer treatment. These therapies have been approved as first-line treatment for certain types of tumors, but their overall clinical efficacy is limited due to tumor heterogeneity and therapy resistance. Predicting patient-specific responses to immunotherapeutic drugs is crucial for personalized treatment and better outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Zhaolian Lu, Beina Nie, Weiwei Zhai, Zheng Hu
Summary: This study discusses the genetic and epigenetic alterations in cancer evolution, the advantages and challenges of using organoids to study cancer evolution, and proposes the establishment of an experimental evolutionary model to study tumor evolution dynamics and patterns over time.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Review
Pharmacology & Pharmacy
Ren Xu, Xiaotao Zhou, Shike Wang, Christine Trinkle
Summary: Tumor development and progression rely on signals from the tumor microenvironment, and recent advances in 3D culture and patient-derived tumor organoid models provide valuable tools for studying cancer development, treatment, and drug response.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
So-Dam Jang, Jeeyeun Song, Hyun-Ah Kim, Chang-Nim Im, Iftikhar Ali Khawar, Jong Kook Park, Hyo-Jeong Kuh
Summary: The study successfully established a 3D PDAC tumor model for evaluating the effectiveness of chemotherapeutic drugs, showing potential anti-invasive effects of anti-cancer agents.
Review
Immunology
Nicoletta Manduca, Ester Maccafeo, Ruggero De Maria, Antonella Sistigu, Martina Musella
Summary: Cancer immunotherapy, despite showing extended progression-free survival in cancer treatment compared to conventional therapies, is effective in only a minority of patients. To improve its applicability, it is crucial to overcome obstacles such as the lack of preclinical models that accurately depict the local tumor microenvironment (TME), which significantly influences disease onset, progression, and response to therapy. This review provides a comprehensive overview of current 3D models, including tumor spheroids, organoids, and immune Tumor-on-a-Chip models, that mimic the complexity and dynamics of the TME. It emphasizes the importance of understanding the TME as a major target in anticancer therapy and highlights the advantages, translational potentials, challenges, and limitations of these models.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Michela Cortesi, Michele Zanoni, Francesca Pirini, Maria Maddalena Tumedei, Sara Ravaioli, Ilario Giovanni Rapposelli, Giovanni Luca Frassineti, Sara Bravaccini
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to immune suppression and the tumor microenvironment. This review explores the interplay between senescent and non-senescent cell types and their impact on PDAC progression. The non-tumoral cells in the tumor microenvironment influence key aspects of tumor growth, metabolism, cell death, and treatment resistance. Understanding these interactions is crucial for PDAC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Michele Zanoni, Alba Clara Sarti, Alice Zamagni, Michela Cortesi, Sara Pignatta, Chiara Arienti, Michela Tebaldi, Anna Sarnelli, Antonino Romeo, Daniela Bartolini, Luigino Tosatto, Elena Adinolfi, Anna Tesei, Francesco Di Virgilio
Summary: Glioblastoma (GBM) is the most lethal brain tumor in adults and is often treated with radiation and temozolomide. However, relapse is common. This study found that after radiation treatment, ATP is released into the tumor microenvironment, activating P2X7 receptors. Different GBM cells vary in P2X7 isoform expression and sensitivity to extracellular ATP. Radiation treatment causes changes in P2X7 isoform expression, leading to cell death and overexpression of stemness and senescence markers. Blocking P2X7 receptors during post-irradiation recovery enhances radiation-dependent cytotoxicity. These findings suggest that P2X7 receptor isoforms play a role in radiation resistance in GBM cells.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Valentina Vultaggio-Poma, Simonetta Falzoni, Paola Chiozzi, Alba Clara Sarti, Elena Adinolfi, Anna Lisa Giuliani, Alejandro Sanchez-Melgar, Paola Boldrini, Michele Zanoni, Anna Tesei, Paolo Pinton, Francesco Di Virgilio
Summary: Nutrient deprivation promotes the release of extracellular ATP and leads to the accumulation of ATP-laden microparticles and naked mitochondria in the tumor microenvironment.
Review
Oncology
Beatrice Aramini, Valentina Masciale, Chiara Arienti, Massimo Dominici, Franco Stella, Giovanni Martinelli, Francesco Fabbri
Summary: The roles and connections of small molecules such as cancer stem cells, circulating tumor cells, and cancer-associated fibroblasts in solid tumors have been under-debated but of significant interest in recent decades. These molecules may play a role in tumor recurrence, drug resistance, and treatment response, but their mechanisms and molecular pathways are still unknown. Defining new molecules to fight against cancer is of great interest to the scientific community. Cancer stem cells, circulating tumor cells, and cancer-associated fibroblasts play important roles in the tumor microenvironment, and discovering biomarkers related to these cell populations and defining the network among them and the tumor microenvironment are becoming increasingly important.
Review
Medicine, General & Internal
Michele Zanoni, Sara Bravaccini, Francesco Fabbri, Chiara Arienti
Summary: Aldehyde dehydrogenases (ALDHs) are detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. ALDHs have various functions in cancer stem cells and immune cells, playing a crucial role in cancer treatment.
FRONTIERS IN MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Michela Cortesi, Michele Zanoni, Roberta Maltoni, Sara Ravaioli, Maria Maddalena Tumedei, Francesca Pirini, Sara Bravaccini
Summary: This article summarizes the important role of Trop2 in breast cancer and discusses the therapeutic strategies targeting Trop2, especially the use of antibody-drug conjugates.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Anna Tesei, Michela Cortesi, Martina Bedeschi, Noemi Marino, Giacomo Rossino, Roberta Listro, Daniela Rossi, Pasquale Linciano, Simona Collina
Summary: Different pathological conditions, including viral infections and cancer, can severely damage the cell by causing endoplasmic reticulum (ER) stress. In particular, coronavirus infections, such as COVID-19, result in ER stress due to the synthesis of large amounts of viral glycoproteins and disruption of ER homeostasis. ER stress plays a crucial role in the viral life cycle and tumor growth, metastasis, and response to therapies in cancer. Researchers have identified the antiplatelet agent ticlopidine as a potential intervention for ER stress induced by viral infections and cancer.
Article
Radiology, Nuclear Medicine & Medical Imaging
Ilaria De Santis, Michele Zanoni, Sara Pignatta, Pasquale Longobardi, Anna Tesei, Alessandro Bevilacqua
Summary: This study used automated quantitative imaging to investigate the distribution of RNA:DNA hybrids in HeLa cells under different oxygen pressures or exposed to different ionizing radiation doses. The results showed that alteration of culture oxygenation increased the presence of hybrids in the cytoplasm, especially in a hyperoxic environment where hybrids gathered at the cell membrane. Ionizing radiations did not increase hybrids, but dose-dependent effects were still observed with a threshold dose of 7.5 Gy for significant reduction in hybrids.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Review
Cell Biology
Martina Bedeschi, Noemi Marino, Elena Cavassi, Filippo Piccinini, Anna Tesei
Summary: Prostate cancer is a common cancer in European males and androgen deprivation therapy is the standard treatment. However, resistance to this therapy has led to cancer progression and long-term side effects. Studies have shown that cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment (TME) and targeting them could be a potential therapeutic approach to overcome therapy resistance in prostate cancer.
Editorial Material
Immunology
Jenny Bulgarelli, Sara Pignatta, Massimiliano Petrini, Laura Ridolfi