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Integrating the Tumor Microenvironment into Cancer Therapy

1
Department of Pathology, Medical School, University of Valencia—INCLIVA Biomedical Health Research Institute, 46010 Valencia, Spain
2
Low Prevalence Tumors, Centro de investigación biomédica en red de cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
3
Department of Oncology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain
4
Department of Pathology, Hospital de Tortosa Verge de la Cinta, Catalan Institute of Health, Institut d’Investigació Sanitària Pere Virgili (IISPV), 43500 Tortosa, Spain
5
Department of Morphological Science, Medical School, Rovira i Virgili University, 43201 Reus, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(6), 1677; https://doi.org/10.3390/cancers12061677
Received: 18 May 2020 / Revised: 11 June 2020 / Accepted: 18 June 2020 / Published: 24 June 2020
(This article belongs to the Section Tumor Microenvironment)
Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression. Indeed, growing evidence is emerging on the impact of the gut microbiota, metabolism, biomechanics, and the neuroimmunological axis on cancer. Thus, external factors capable of influencing the entire body system, such as emotional stress, surgery, or psychosocial factors, must be taken into consideration for enhanced management and treatment of cancer patients. In this article, we review prognostic and predictive biomarkers, as well as their potential evaluation and quantitative analysis. Our overarching aim is to open up new fields of study and intervention possibilities, within the framework of an integral vision of cancer as a functional tissue with the capacity to respond to different non-cytotoxic factors, hormonal, immunological, and mechanical forces, and others inducing stroma and tumor reprogramming. View Full-Text
Keywords: immune therapy; metabolism; microbiota; biomarker discovery; prognostic tools; vitamin D3; stromal reprogramming; mitochondria; mechanotransduction; metformin immune therapy; metabolism; microbiota; biomarker discovery; prognostic tools; vitamin D3; stromal reprogramming; mitochondria; mechanotransduction; metformin
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Sanegre, S.; Lucantoni, F.; Burgos-Panadero, R.; de La Cruz-Merino, L.; Noguera, R.; Álvaro Naranjo, T. Integrating the Tumor Microenvironment into Cancer Therapy. Cancers 2020, 12, 1677.

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