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      Organ tropism in solid tumor metastasis: an updated review

      1 , 2
      Future Oncology
      Future Medicine Ltd

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          Abstract

          Tumors are equipped with a highly complex machinery of interrelated events so as to adapt to hazardous conditions, preserve a growing cell mass and thrive at the site of metastasis. Tumor cells display metastatic propensity toward specific organs where the stromal milieu is appropriate for their further colonization. Effective colonization relies on the plasticity of tumor cells in adapting to the conditions of the new area by reshaping their epigenetic landscape. Breast cancer cells, for instance, are able to adopt brain-like or epithelial/osteoid features in order to pursue effective metastasis into brain and bone, respectively. The aim of this review is to discuss recent insights into organ tropism in tumor metastasis, outlining potential strategies to address this driver of tumor aggressiveness.

          Abstract

          Lay abstract

          Tumors of solid organs choose specific organs as their secondary foci; tumor cells dissociated from the primary tumor are not able to grow in all body tissues, so there are a number of organs designated to provide an appropriate growth environment for colonization of these detached cells. Brain, lymph nodes, bone, liver and lung are the five most common sites of metastasis for solid tumors. These organs attract disseminated tumor cells by displaying characteristics that can be either specific or shared among them. Detection of the promoters of organ tropism in cancer metastasis and their targeting can be a promising strategy for reducing the possibility of tumor dispersion.

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          Most cited references151

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          Transforming Growth Factor-β Signaling in Immunity and Cancer

          Transforming growth factor (TGF)-β is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Perturbations in TGF-β signaling underlie inflammatory diseases and promote tumor emergence. TGF-β is also central to immune suppression within the tumor microenvironment, and recent studies have revealed roles in tumor immune evasion and poor responses to cancer immunotherapy. Here, we present an overview of the complex biology of the TGF-β family and its context-dependent nature. Then, focusing on cancer, we discuss the roles of TGF-β signaling in distinct immune cell types and how this knowledge is being leveraged to unleash the immune system against the tumor.
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            Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges

            Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one. Immunotherapy relies on the accumulation and activity of immune effector cells within the TME, and immune responses and vascular normalization seem to be reciprocally regulated. Thus, combining antiangiogenic therapies and immunotherapies might increase the effectiveness of immunotherapy and diminish the risk of immune-related adverse effects. In this Perspective, we outline the roles of VEGF and ANG2 in tumour immune evasion and progression, and discuss the evidence indicating that antiangiogenic agents can normalize the TME. We also suggest ways that antiangiogenic agents can be combined with immune-checkpoint inhibitors to potentially improve patient outcomes, and highlight avenues of future research.
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              Is Open Access

              Molecular principles of metastasis: a hallmark of cancer revisited

              Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Future Oncology
                Future Oncology
                Future Medicine Ltd
                1479-6694
                1744-8301
                May 2021
                May 2021
                : 17
                : 15
                : 1943-1961
                Affiliations
                [1 ]Cancer & Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, 66177‐13446, Iran
                [2 ]Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, 66177‐13446, Iran
                Article
                10.2217/fon-2020-1103
                33728946
                9ffb8188-408a-4bbb-b5cd-c2864fc44491
                © 2021
                History

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