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      Tumour dormancy and clinical implications in breast cancer

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          Abstract

          The aim of adjuvant therapy in breast cancer is to reduce the risk of recurrence. Some patients develop metastases many years after apparently successful treatment of their primary cancer. Tumour dormancy may explain the long time between initial diagnosis and treatment of cancer, and occurrence of relapse. The regulation of the switch from clinical dormancy to cancer regrowth in locoregional and distant sites is poorly understood. In this review, we report some data supporting the existence of various factors that may explain cancer dormancy including genetic and epigenetic changes, angiogenic switch, microenvironment, and immunosurveillance. A better definition and understanding of these factors should allow the identification of patients at high risk of relapse and to develop new therapeutic strategies in order to improve prognosis.

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          Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.

          Daniel Hicklin, Lee Ellis (2005)
          New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.
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            Regulatory T cells, tumour immunity and immunotherapy.

            Weiping Zou (2006)
            Tumours express a range of antigens, including self-antigens. Regulatory T cells are crucial for maintaining T-cell tolerance to self-antigens. Regulatory T cells are thought to dampen T-cell immunity to tumour-associated antigens and to be the main obstacle tempering successful immunotherapy and active vaccination. In this Review, I consider the nature and characteristics of regulatory T cells in the tumour microenvironment and their potential multiple suppressive mechanisms. Strategies for therapeutic targeting of regulatory T cells and the effect of regulatory T cells on current immunotherapeutic and vaccine regimens are discussed.
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              Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression.

              Lars Holmgren, Michael O'Reilly, Judah Folkman (1995)
              In cancer patients, dormant micrometastases are often asymptomatic and clinically undetectable, for months or years, until relapse. We have studied dormant lung metastases under angiogenesis suppression in mice. The metastases exhibited rapid growth when the inhibition of angiogenesis was removed. Tumour cell proliferation, as measured by bromodeoxyuridine incorporation and immunohistochemical staining proliferating cell nuclear antigen, was not significantly different in dormant and growing metastases. However, tumour cells of dormant metastases exhibited a more than threefold higher incidence of apoptosis. These data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ecancermedicalscience
                Journal ID (iso-abbrev): Ecancermedicalscience
                Journal ID (publisher-id): ecancermedicalscience
                Title: ecancermedicalscience
                Publisher: Cancer Intelligence
                ISSN (Electronic): 1754-6605
                Publication date Collection: 2013
                Publication date (Electronic): 21 May 2013
                Volume: 7
                Electronic Location Identifier: 320
                Affiliations
                [] Early Drug Development for Innovative Therapy Division, European Institute of Oncology, Milan, Italy
                Author notes
                Correspondence to: L Gelao. lucia.gelao@ 123456ieo.it
                Article
                Publisher ID: can-7-320
                DOI: 10.3332/ecancer.2013.320
                PMC ID: 3660156
                PubMed ID: 23717341
                SO-VID: 128f7f74-f74e-44bc-a966-4fc742a30c5f
                Copyright © © the authors; licensee ecancermedicalscience.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 February 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tumor dormancy,breast cancers,angiogenesis,microenvironment,immune surveillance
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tumor dormancy, breast cancers, angiogenesis, microenvironment, immune surveillance

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