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      Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

      review-article
      Author(s): ,
      Publication date (Electronic):
      Journal: Cancer Management and Research
      Publisher: Dove Medical Press
      Keywords: HIF-1, cancer, chemoresistance, signaling, apoptosis

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          Abstract

          Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance.

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          Epithelial-mesenchymal transitions in development and disease.

          Jean Paul Thiery, Hervé Acloque, Ruby Y J Huang … (2009)
          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
          Article 0 comments Cited 3728 times – based on 0 reviews     Review now
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            Hypoxia in cancer: significance and impact on clinical outcome.

            Peter Vaupel, Arnulf Mayer (2007)
            Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O(2) sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous bioreductive drugs. In many - albeit not in all - studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.
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              Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.

              G. L. Semenza (2010)
              Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared with normal tissue, and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): Cancer Management and Research
                Title: Cancer Management and Research
                Publisher: Dove Medical Press
                ISSN (Electronic): 1179-1322
                Publication date Collection: 2015
                Publication date (Electronic): 12 August 2015
                Volume: 7
                Pages: 253-264
                Affiliations
                Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA
                Author notes
                Correspondence: Mauricio J Reginato, Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA, USA, Tel +1 215 762 3554, Fax +1 215 762 4452, Email mauricio.reginato@ 123456drexelmed.edu
                Article
                Publisher ID: cmar-7-253
                DOI: 10.2147/CMAR.S58285
                PMC ID: 4542411
                PubMed ID: 26316817
                SO-VID: 1b0685e4-65c1-4b2a-927b-63cc3b3ace36
                Copyright © © 2015 Karakashev and Reginato. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License
                License:

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hif-1,cancer,chemoresistance,signaling,apoptosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hif-1, cancer, chemoresistance, signaling, apoptosis

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