mTOR Pathway and mTOR Inhibitors in Cancer Therapy (Cancer Drug Discovery and Development)

mTOR Pathway and mTOR Inhibitors in Cancer Therapy provides an up-to-date survey of the rapidly advancing field of cancer therapy. Our understanding of the mechanisms involved in cancer genesis and progression underwent unprecedented expansion during the last decade, opening a new era of cancer treatment – targeted therapy. The surge in this area results in no small part from studies conducted jointly by basic health scientists and clinical investigators. It is our hope that this book will help foster even further collaboration between investigators in these two disciplines. In this work, experts in TOR signaling have contributed in two thematic areas: mTOR Signaling and Cancer Therapy (chapters 1 - 8) and Therapeutic Targeting Downstream of mTOR (chapter 9 – 13). All chapters of mTOR Pathway and mTOR Inhibitors in Cancer Therapy are completely new or have been extensively updated by their authors; and we are indebted to all authors who have exemplified the links between these 2 thematic areas. The main objective of this book is to provide an up-to-date survey of the rapidly advancing eld of cancer therapy. Moreover, since our knowledge in this area rapidly evolves, some data have got obsolete during the process of book editing. Our understanding of the mechanisms involved in cancer genesis and progression underwent unprecedented expansion during the last decade, opening a new era of cancer treatment – targeted therapy. The surge in this area results in no small part from studies conducted jointly by basic health scientists and clinical investigators. It is our hope that this book will help foster even further collaboration between investigators in these two disciplines. The target of rapamycin (TOR) was rst identi ed in Saccharomyces cerevisiae and subsequently in mammals (mTOR) as a conserved atypical serine/threonine kinase. In mammalian cells, mTOR exists in at least two multi-protein complexes that have critical roles in regulating cellular homeostasis and survival. As with many other areas of science, discovery of TOR signaling was fortuitous. Rapamycin was isolated as a product of the soil bacteria Streptomyces hygroscopicus, identi ed in a soil sample taken from the island of Rapa Nui (Easter Island). Rapamycin was rst discovered to be a potent antifungal agent and next as an immune suppressive drug. It was only later that it was found to be active as an antitumor agent in non-clinical models; although it was not developed for this indication. The history of rapamycin presents one of the rst examples of chemical genetics. Front Matter....Pages i-xii mTORC1: A Signaling Integration Node Involved in Cell Growth....Pages 1-36 The Regulation of the IGF-1/mTOR Pathway by the p53 Tumor Suppressor Gene Functions....Pages 37-48 mTOR Signaling in Angiogenesis....Pages 49-74 mTORC1 Signaling and Hypoxia....Pages 75-97 mTOR Signaling in Glioblastoma: Lessons Learned from Bench to Bedside....Pages 99-111 mTOR and Cancer Therapy: General Principles....Pages 113-131 mTOR and Cancer Therapy: Clinical Development and Novel Prospects....Pages 133-148 Drug Combinations as a Therapeutic Approach for mTORC1 Inhibitors in Human Cancer....Pages 149-178 Downstream Targets of mTORC1....Pages 179-200 Downstream of mTOR: Translational Control of Cancer....Pages 201-216 Genome-Wide Analysis of Translational Control....Pages 217-236 Translational Control of Cancer: Implications for Targeted Therapy....Pages 237-255 Downstream from mTOR: Therapeutic Approaches to Targeting the eIF4F Translation Initiation Complex....Pages 257-285 Back Matter....Pages 287-301 Annotation mTOR Pathway and mTOR Inhibitors in Cancer Therapy provides an up-to-date survey of the rapidly advancing field of cancer therapy. Our understanding of the mechanisms involved in cancer genesis and progression underwent unprecedented expansion during the last decade, opening a new era of cancer treatment €“ targeted therapy. The surge in this area results in no small part from studies conducted jointly by basic health scientists and clinical investigators. It is our hope that this book will help foster even further collaboration between investigators in these two disciplines. In this work, experts in TOR signaling have contributed in two thematic areas: mTOR Signaling and Cancer Therapy (chapters 1 - 8) and Therapeutic Targeting Downstream of mTOR (chapter 9 €“ 13). All chapters of mTOR Pathway and mTOR Inhibitors in Cancer Therapy are completely new or have been extensively updated by their authors; and we are indebted to all authors who have exemplified the links between these 2 thematic areas