The Roles of Reactive Oxygen Species and Autophagy in Mediating the Tolerance of Tumor Cells to Cycling Hypoxia
Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient outcome. A substantial fraction of tumor cells experience cycling hypoxia, characterized by transient episodes of hypoxia and reoxygenation. These cells are under a unique burden of stress, mediated by excessive production of reactive oxygen species (ROS). Cellular components damaged by ROS can be cleared by autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to inhibition of autophagy and its upstream regulatory pathways. Activation of the PERK-mediated signaling arm of the unfolded protein response during hypoxia plays a cri...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Marianne Koritzinsky, Bradly G. Wouters Source Type: research
Tumors as Organs: Biologically Augmenting Radiation Therapy by Inhibiting Transforming Growth Factor β Activity in Carcinomas
Transforming growth factor β (TGFβ) plays critical roles in regulating a plethora of physiological processes in normal organs, including morphogenesis, embryonic development, stem cell differentiation, immune regulation, and wound healing. Though considered a tumor suppressor, TGFβ is a critical mediator of tumor microenvironment, in which it likewise mediates tumor and stromal cell phenotype, recruitment, inflammation, immune function, and angiogenesis. The fact that activation of TGFβ is an early and persistent event in irradiated tissues and that TGFβ signaling controls effective DNA damage response provides a new ...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Shisuo Du, Mary Helen Barcellos-Hoff Source Type: research
Characterization of the Stem Cell Niche and Its Importance in Radiobiological Response
Normal tissues are organized hierarchically with a small number of stem cells, able to self-renew and give rise to all the differentiated cells found in the respective specialized tissues. The undifferentiated, multipotent state of normal stem cells is codetermined by the constituents of a specific anatomical space that hosts the normal stem cell population, called the “stem cell niche.” Radiation interferes not only with the stem cell population but also with the stem cell niche, thus modulating a complex regulatory network. There is now mounting experimental evidence that many solid cancers share this hierarchical or...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Frank Pajonk, Erina Vlashi Source Type: research
Introduction: Tumor as an Organ
In this issue of Seminars in Radiation Oncology, we focus on the theme of tumors as dysfunctional organs. Hanahan and Weinberg have pointed out in their most recent “Hallmarks of Cancer” review that tumors contain communities of cells and stromal elements that work in concert to promote tumor cell growth, angiogenesis, invasion, and metastasis as well as immune system evasion. The features of this microenvironment also influence the efficacy of therapy. As such, an understanding of the tumor microenvironment is highly relevant to the development of new therapeutic targets. The cover of this special issue highlights the...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Mark W. Dewhirst Source Type: research
Understanding the Tumor Microenvironment and Radioresistance by Combining Functional Imaging With Global Gene Expression
The objective of this review is to present an argument for performing joint analyses between functional imaging with global gene expression studies. The reason for making this link is that tumor microenvironmental influences on functional imaging can be uncovered. Such knowledge can lead to (1) more informed decisions regarding how to use functional imaging to guide therapy and (2) discovery of new therapeutic targets. As such, this approach could lead to identification of patients who need aggressive treatment tailored toward the phenotype of their tumor vs those who could be spared treatment that carries risk for more no...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Mark W. Dewhirst, Jen-Tsan Chi Source Type: research
Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy
The death of all the cancer cells in a tumor is the ultimate goal of cancer therapy. Therefore, much of the current effort in cancer research is focused on activating cellular machinery that facilitates cell death such as factors involved in causing apoptosis. However, recently, a number of studies point to some counterintuitive roles for apoptotic caspases in radiation therapy as well as in tissue regeneration. It appears that a major function of apoptotic caspases is to facilitate tissue regeneration and tumor cell repopulation during cancer therapy. Because tumor cell repopulation has been shown to be important for loca...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Mary A. Zimmerman, Qian Huang, Fang Li, Xinjiang Liu, Chuan-Yuan Li Source Type: research
Inhibiting Vasculogenesis After Radiation: A New Paradigm to Improve Local Control by Radiotherapy
Tumors are supported by blood vessels, and it has long been debated whether their response to irradiation is affected by radiation damage to the vasculature. We have shown in preclinical models that, indeed, radiation is damaging to the tumor vasculature and strongly inhibits tumor angiogenesis. However, the vasculature can recover by colonization from circulating cells, primarily proangiogenenic CD11b+ monocytes or macrophages from the bone marrow. This secondary pathway of blood vessel formation, known as vasculogenesis, thus acts to restore the tumor vasculature and allows the tumor to recur following radiation. The sti...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Brown J. Martin Source Type: research
Radiation as an Immune Modulator
Radiation therapy is currently one of the most widely utilized treatment strategies in the clinical management of cancer. Classically, radiation therapy was developed as an anticancer treatment on the basis of its capacity to induce DNA double strand breaks in exposed cancer cells, ultimately resulting in tumor cell death. Recently, our understanding of radiation effects has expanded widely in terms of the consequences of radiation-induced tumor cell death and the pertinent cells, signaling pathways, and molecular sensors that modify the tumor response to radiation. It is now well accepted that inflammation plays a complex...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Byron Burnette, Ralph R. Weichselbaum Source Type: research
Optimization of Tumor Radiotherapy With Modulators of Cell Metabolism: Toward Clinical Applications
Most solid tumors are characterized by unstable perfusion patterns, creating regions of hypoxia that are detrimental to radiotherapy treatment response. Because postsurgical radiotherapy, alone or in combination with other interventions, is a first-line treatment for many malignancies, strategies aimed at homogeneously increasing tumor pO2 have been the focus of intense research over the past decades. Among other approaches of demonstrable clinical and preclinical utility, this review focuses on those directly targeting oxygen consumption to redirect oxygen from a metabolic fate to the stabilization of radiation-induced DN...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Pierre Danhier, Christophe J. De Saedeleer, Oussama Karroum, Géraldine De Preter, Paolo E. Porporato, Bénédicte F. Jordan, Bernard Gallez, Pierre Sonveaux Source Type: research
The Roles of Reactive Oxygen Species and Autophagy in Mediating the Tolerance of Tumor Cells to Cycling Hypoxia
Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient outcome. A substantial fraction of tumor cells experience cycling hypoxia, characterized by transient episodes of hypoxia and reoxygenation. These cells are under a unique burden of stress, mediated by excessive production of reactive oxygen species (ROS). Cellular components damaged by ROS can be cleared by autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to inhibition of autophagy and its upstream regulatory pathways. Activation of the PERK-mediated signaling arm of the unfolded protein response during hypoxia plays a cri...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Marianne Koritzinsky, Bradly G. Wouters Source Type: research
Tumors as Organs: Biologically Augmenting Radiation Therapy by Inhibiting Transforming Growth Factor β Activity in Carcinomas
Transforming growth factor β (TGFβ) plays critical roles in regulating a plethora of physiological processes in normal organs, including morphogenesis, embryonic development, stem cell differentiation, immune regulation, and wound healing. Though considered a tumor suppressor, TGFβ is a critical mediator of tumor microenvironment, in which it likewise mediates tumor and stromal cell phenotype, recruitment, inflammation, immune function, and angiogenesis. The fact that activation of TGFβ is an early and persistent event in irradiated tissues and that TGFβ signaling controls effective DNA damage response provides a new ...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Shisuo Du, Mary Helen Barcellos-Hoff Source Type: research
Characterization of the Stem Cell Niche and Its Importance in Radiobiological Response
Normal tissues are organized hierarchically with a small number of stem cells, able to self-renew and give rise to all the differentiated cells found in the respective specialized tissues. The undifferentiated, multipotent state of normal stem cells is codetermined by the constituents of a specific anatomical space that hosts the normal stem cell population, called the “stem cell niche.” Radiation interferes not only with the stem cell population but also with the stem cell niche, thus modulating a complex regulatory network. There is now mounting experimental evidence that many solid cancers share this hierarchical or...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Frank Pajonk, Erina Vlashi Source Type: research
Introduction: Tumor as an Organ
In this issue of Seminars in Radiation Oncology, we focus on the theme of tumors as dysfunctional organs. Hanahan and Weinberg have pointed out in their most recent “Hallmarks of Cancer” review that tumors contain communities of cells and stromal elements that work in concert to promote tumor cell growth, angiogenesis, invasion, and metastasis as well as immune system evasion. The features of this microenvironment also influence the efficacy of therapy. As such, an understanding of the tumor microenvironment is highly relevant to the development of new therapeutic targets. The cover of this special issue highlights the...
Source: Seminars in Radiation Oncology - September 7, 2013 Category: Cancer & Oncology Authors: Mark W. Dewhirst Source Type: research
Cancer Control and Complications of Salvage Local Therapy After Failure of Radiotherapy for Prostate Cancer: A Systematic Review
The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachythe...
Source: Seminars in Radiation Oncology - June 10, 2013 Category: Cancer & Oncology Authors: Arti Parekh, Powell L. Graham, Paul L. Nguyen Source Type: research
Adjuvant Versus Salvage Radiotherapy for High-Risk Prostate Cancer Patients
Radiotherapy (RT) after prostatectomy may potentially eradicate any residual localized microscopic disease in the prostate bed. The current dilemma is whether to deliver adjuvant RT solely on the basis of high-risk pathology (pT3 or positive margins), but in the absence of measurable prostate-specific antigen, or whether early salvage radiotherapy (SRT) would yield equivalent outcomes. Although the results of current randomized trials answering this very question remain years away, the best evidence to date supports early SRT as the better strategy. In terms of SRT, the pooled evidence reveals that one should initiate RT a...
Source: Seminars in Radiation Oncology - June 10, 2013 Category: Cancer & Oncology Authors: Christopher R. King Source Type: research
