This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation.
Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.
Introduction: The Unfolded Protein Response.- Endoplasmic Reticulum
Stress Signaling During Development.- Regulation of the Unfolded Protein
Response and its Roles in Tumorigenesis and Cancer Therapy.- ATF4, Hypoxia
and Treatment Resistance in Cancer.- Role of Protein Translation in the
Unfolded Protein Response.- Roles of Spliced and Unspliced XBP1 in Breast
Cancer.- The Unfolded Protein Response in Triple-Negative Breast Cancer.- The
Unfolded Protein Response as an Integrator of Response to Endocrine Therapy
in Estrogen Receptor Positive Breast Cancer.- Outside the Endoplasmic
Reticulum: Non-Canonical GRP78 Signaling.- Autophagy and the Unfolded Protein
Response in Neurodegenerative Diseases.- Index.
Robert Clarke, PhD, DSc, FRSBiol, FRSChem, FRSMed is Professor of Oncology at Georgetown University (Washington, DC, USA). He is Dean for Research at Georgetown University Medical Center (GUMC), home to over 80% of sponsored research at Georgetown University. Dr. Clarke is also Director of the Biomedical Graduate Research Organization, one of four academic units within GUMC. A member of the Georgetown-Lombardi Comprehensive Cancer Center, he is currently Co-Leader of the Breast Cancer Program.
Dr. Clarke earned a DSc in 1999, a PhD in 1986, and a MSc in 1982 (each in Biochemistry) from the Queens University of Belfast, Northern Ireland, and a BSc (Biological Sciences) in 1980 from the University of Ulster, Northern Ireland. He completed his postdoctoral training as a Breast Cancer Study Group Fellow with Dr. Marc E. Lippman at the National Cancer Institute (National Institutes of Health, Bethesda, MD, USA). In 1989, Dr. Clarke joined the Department of Physiology & Biophysics at Georgetown University. He served as Secretary/Treasurer of the Georgetown University Faculty Senate from 2004-2007.
Dr. Clarke is an elected Fellow of the Royal Society of Chemistry (UK), the Royal Society of Medicine (UK), and the Royal Society of Biology (UK). An internationally recognized leader in breast cancer research, he was honored among the 100 most frequently published breast cancer researchers of the 20th Century at the 23rd San Antonio Breast Cancer Symposium (2000). Dr. Clarke completed full terms as chair of both the National Institutes of Health grant peer-review study sections National Center for Complementary and Alternative Medicine: Basic Science (2002-2008) and National Cancer Institute: Basic Mechanisms of Cancer Therapeutics (2011-2013), and he has chaired several NIH Special Emphasis Panels and grant review panels for the US Army Medical Research and Materiel Command (Breast Cancer Research Program). Regularly invited to speak about his research, he completed a three year term as the NCI-SigmaXi Distinguished Lecturer in 2014. Currently, Dr. Clarke is a Senior Editor for the journal Cancer Research, and he serves on the editorial boards of over a dozen international scientific journals.
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