Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review
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Cellular and Molecular Life Sciences
REVIEW
Relevance of humanized three‑dimensional tumor tissue models: a descriptive systematic literature review D. Contartese1 · Francesca Salamanna1 · F. Veronesi1 · M. Fini1 Received: 11 September 2019 / Revised: 25 March 2020 / Accepted: 30 March 2020 © Springer Nature Switzerland AG 2020
Abstract Despite numerous advances in tumor screening, diagnosis, and treatment, to date, tumors remain one of the leading causes of death, principally due to metastasis and the physiological damage produced by tumor growth. Among the main limits related to the study of tumor physiology there is the complex and heterogeneity nature of its environment and the absence of relevant, simple and inexpensive models able to mimic the biological processes occurring in patients allowing the correct clinical translation of results. To enhance the understanding of the mechanisms of tumors and to develop and evaluate new therapeutic approaches the set-up of advanced and alternative models is mandatory. One of the more translational approaches seems to be the use of humanized three-dimensional (3D) tissue culture. This model allows to accurately mimic tumor morphology and biology, maintaining the native microenvironment without any manipulation. However, little is still known on the real clinical relevance of these models for the study of tumor mechanisms and for the screening of new therapy. The aim of this descriptive systematic literature review was to evaluate and summarize the current knowledge on human 3D tumor tissue culture models. We reviewed the strategies employed by researchers to set-up these systems, also considering the different approaches and culture conditions used. All these aspects greatly contribute to the existing knowledge on tumors, providing a specific link to clinical scenarios and making the humanized 3D tumor tissue models a more attractive tool both for researchers and clinicians. Keywords Tumor · Metastasis · Tissue culture · Three-dimensional model · Clinical translation · Systematic literature review
Introduction Tumors represent a type of multifaceted pathological condition, where normal cells begin to be hyper-proliferative and start the expression of a number of factors, i.e., cytokines, chemokines and growth factors, involved in cell proliferation, invasion and metastasis [1]. To date, surgery associated to standard chemotherapeutic protocols and radiotherapy represents the first-line treatment for most tumors, with a significant increase in survival rates [2, 3]. Immunotherapy, i.e., immune checkpoint blockade, cancer vaccines, and adoptive cell therapy, also allows an increase in anti-tumor immune responses and an improvement of the patient’s * Francesca Salamanna [email protected] 1
Laboratory Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy
clinical outcomes with minimal toxicity [4]. However, tumors still continue to represent one of the main causes of mortality [5, 6] principally du
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