mTOR_Pathway_and_mTOR_Inhibitors_in Cancer_Therapy
(Cancer_Drug_Discovery_and_Development)
By
Vitaly_A._Polunovsky,_Peter_J._Houghton
(Cancer_Drug_Discovery_and_Development)
By
Vitaly_A._Polunovsky,_Peter_J._Houghton
- Publisher: H_um*ana_Press
- Number Of Pages: 235
- Publication Date: 2010-08-01
- ASIN: 16_03_2727_04
- EAN: 978_16032_72704
Preface
The main objective of this book is to provide an up-to-date survey of the rapidly advancing field 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 first identified 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, identified in a soil sample taken from the island of Rapa Nui (Easter Island). Rapamycin was first 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 main objective of this book is to provide an up-to-date survey of the rapidly advancing field 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 first identified 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, identified in a soil sample taken from the island of Rapa Nui (Easter Island). Rapamycin was first 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.
Contents
mTORC1: A Signaling Integration Node Involved in Cell Growth . ......................... 1 a
Neil_Kubica and John_Blenis
The Regulation of the IGF-1/mTOR Pathway by the p53 Tumor
Suppressor Gene Functions . . . . . . . . . . . . . . . . . . . . . ................................. . . . 37 a
Zhaohui_Feng and Arnold_J. Levine
mTOR Signaling in Angiogenesis . . . . . . . . . . . . . . . . . . . ................................. . . 49 a
Henry_Mead, Mirjana_Zeremski, and Markus_Guba
m*TORC1 Signaling and Hypoxia . . . . . . . . . . . . . . . . .................................. . . . . . 75 a
James_Brugarolas
mTOR Signaling in Glioblastoma: Lessons Learned from Bench
to Bedside . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........................................ . . . . 99 a
David_Akhavan and Paul_S._Mischel
mTOR and Cancer Therapy: General Principles . . . . . . ............................ . . . . . . 113 a
Peter_J._Houghton
mTOR_and Cancer_Therapy: Clinical_Development_and_Novel
Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........................................ . . . . 133 a
Sandrine_Faivre, Thomas_Decaens, and Eric_Raymond
Drug_Combinations as a Therapeutic_Approach for_mTORC1
Inhibitors_in_Human_Cancer . . . . . . . . . . . . . . . . . ................................... . . . . . . 149 a
Madlaina_Breuleux and Heidi_A._Lane
Downstream Targets of mTORC1 . . . . . . . . . . . . . ................................. . . . . . . . 179 a
Bruno_D. Fonseca_and Christopher_G._Proud
Downstream of_mTOR: Translational_Control of_Cancer . . ......................... . . . . . 201 a
Ryan_J.O. Dowling and Nahum_Sonenberg
Genome-Wide Analysis of Translational_Control . . . . . . . ........................... . . . . . 217 a
Ola_Larsson_and Peter_B._Bitterman
Translational Control of Cancer: Implications for Targeted Therapy . ................... 237 a
Peter_B._Bitterman and Vitaly_A._Polunovsky
Downstream from_mTOR: Therapeutic_Approaches
to Targeting the eIF4F Translation Initiation Complex . . . . . . ........................ . . . 257 a
Jerry_Pelletier and_Jeremy_R._Graff
mTORC1: A Signaling Integration Node Involved in Cell Growth . ......................... 1 a
Neil_Kubica and John_Blenis
The Regulation of the IGF-1/mTOR Pathway by the p53 Tumor
Suppressor Gene Functions . . . . . . . . . . . . . . . . . . . . . ................................. . . . 37 a
Zhaohui_Feng and Arnold_J. Levine
mTOR Signaling in Angiogenesis . . . . . . . . . . . . . . . . . . . ................................. . . 49 a
Henry_Mead, Mirjana_Zeremski, and Markus_Guba
m*TORC1 Signaling and Hypoxia . . . . . . . . . . . . . . . . .................................. . . . . . 75 a
James_Brugarolas
mTOR Signaling in Glioblastoma: Lessons Learned from Bench
to Bedside . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........................................ . . . . 99 a
David_Akhavan and Paul_S._Mischel
mTOR and Cancer Therapy: General Principles . . . . . . ............................ . . . . . . 113 a
Peter_J._Houghton
mTOR_and Cancer_Therapy: Clinical_Development_and_Novel
Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........................................ . . . . 133 a
Sandrine_Faivre, Thomas_Decaens, and Eric_Raymond
Drug_Combinations as a Therapeutic_Approach for_mTORC1
Inhibitors_in_Human_Cancer . . . . . . . . . . . . . . . . . ................................... . . . . . . 149 a
Madlaina_Breuleux and Heidi_A._Lane
Downstream Targets of mTORC1 . . . . . . . . . . . . . ................................. . . . . . . . 179 a
Bruno_D. Fonseca_and Christopher_G._Proud
Downstream of_mTOR: Translational_Control of_Cancer . . ......................... . . . . . 201 a
Ryan_J.O. Dowling and Nahum_Sonenberg
Genome-Wide Analysis of Translational_Control . . . . . . . ........................... . . . . . 217 a
Ola_Larsson_and Peter_B._Bitterman
Translational Control of Cancer: Implications for Targeted Therapy . ................... 237 a
Peter_B._Bitterman and Vitaly_A._Polunovsky
Downstream from_mTOR: Therapeutic_Approaches
to Targeting the eIF4F Translation Initiation Complex . . . . . . ........................ . . . 257 a
Jerry_Pelletier and_Jeremy_R._Graff
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................................ . . . . . . 287
a
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