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      Biological response of cancer cells to radiation treatment

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          Abstract

          Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made toward the understanding of proposed hallmarks of cancer development, care, and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET), total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals) damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE). In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed.

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          Cancer and Radiation Therapy: Current Advances and Future Directions

          In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
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            Models, mechanisms and clinical evidence for cancer dormancy.

            Patients with cancer can develop recurrent metastatic disease with latency periods that range from years even to decades. This pause can be explained by cancer dormancy, a stage in cancer progression in which residual disease is present but remains asymptomatic. Cancer dormancy is poorly understood, resulting in major shortcomings in our understanding of the full complexity of the disease. Here, I review experimental and clinical evidence that supports the existence of various mechanisms of cancer dormancy including angiogenic dormancy, cellular dormancy (G0-G1 arrest) and immunosurveillance. The advances in this field provide an emerging picture of how cancer dormancy can ensue and how it could be therapeutically targeted.
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              When mutants gain new powers: news from the mutant p53 field.

              Ample data indicate that mutant p53 proteins not only lose their tumour suppressive functions, but also gain new abilities that promote tumorigenesis. Moreover, recent studies have modified our view of mutant p53 proteins, portraying them not as inert mutants, but rather as regulated proteins that influence the cancer cell transcriptome and phenotype. This influence is clinically manifested as association of TP53 mutations with poor prognosis and drug resistance in a growing array of malignancies. Here, we review recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association, with a focus on the clinical implications of these findings.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                17 November 2014
                2014
                : 1
                : 24
                Affiliations
                Division of Cellular and Molecular Research, Department of Radiation Oncology, National Cancer Centre Singapore, Singapore
                Author notes

                Edited by: Maria Cecilia Giron, University of Padova, Italy

                Reviewed by: Richard Chahwan, Albert Einstein College of Medicine of Yeshiva University, USA; Arun Bhardwaj, University of South Alabama Mitchell Cancer Institute, USA; Buck Rogers, Washington University in St. Louis, USA

                *Correspondence: Rajamanickam Baskar, Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research, Department of Radiation Oncology, National Cancer Centre, 11- Hospital Drive, Singapore-169610, Singapore e-mail: r.baskar@ 123456nccs.com.sg

                This article was submitted to Cellular Biochemistry, a section of the journal Frontiers in Molecular Biosciences.

                Article
                10.3389/fmolb.2014.00024
                4429645
                25988165
                c9211ae4-628f-4e8f-817e-d9cc8fc21315
                Copyright © 2014 Baskar, Dai, Wenlong, Yeo and Yeoh.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 July 2014
                : 31 October 2014
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 111, Pages: 9, Words: 7762
                Categories
                Chemistry
                Review Article

                cancer cells,radiation,direct dna damage,bystander effect

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