Molecular Biology of Cancer Mechanisms, Targets, and Therapeutics

by Pecorino, Lauren

• ISBN13: 9780199264728
• ISBN10: 0199264724
• Format: Hardcover
• Copyright: 2005-06-02
• Publisher: Oxford University Press

Summary

Many of the cells in our body undergo tightly regulated replication to enable growth to occur, and to ensure that damaged or worn out tissues are replaced. Regulation is mediated via many different mechanisms; it is when these mechanisms fail, and regulation is lost, that cancer can result.Recent advances in molecular cell biology have greatly expanded our understanding of the processes and mechanisms which underpin the regulation of cell replication, and what is happening at the molecular level when these fail.The Molecular Biology of Cancer: Mechanisms, Targets, and Therapeutics offers a fresh approach to the study of the molecular basis of cancer, and shows how our understanding of the defective mechanisms which drive cancer is leading to the development of new targeted therapeutic agents.Opening with an overview of the key hallmarks of cancer as a disease state, the book then leads us through the principal components of the regulatory machinery through which cell division is controlled, and explains how the failure of these components can lead to the onset of cancer. Uniquely,within each chapter, students are shown how this molecular knowledge is being applied to develop new targeted therapeutic strategies.The Molecular Biology of Cancer will prove a valuable resource for any student wishing to gain an insight into the molecular basis of the disease, and possible solutions for its effective control.Companion Web SiteFeatures figures from the book available to download, to facilitate lecture preparation, and a web link library to give students easy access to relevant online resources.

Author Biography

Dr. Lauren Pecorino is Senior Lecturer and Biochemistry Programme Leader, School of Chemical and Life Sciences, University of Greenwich, UK

Table of Contents

PREFACE	xiii
ACKNOWLEDGEMENTS	xvii
1 Introduction	1	(20)
1.1 What is cancer?	1	(3)
1.2 Evidence suggests that cancer is a genetic disease at the cellular level	4	(6)
1.3 Influential factors in human carcinogenesis	10	(3)
1.4 Principles of conventional cancer therapies	13	(1)
1.5 The role of molecular targets in cancer therapies	14	(7)
2 DNA structure and stability: mutations vs. repair	21	(28)
2.1 Gene structure-two parts of a gene: the regulatory region and the coding region	21	(2)
2.2 Mutations	23	(1)
2.3 Carcinogenic agents	24	(12)
2.4 DNA repair and predispositions to cancer	36	(4)
2.5 Conventional therapies: chemotherapy and radiation therapy	40	(9)
3 Regulation of gene expression	49	(20)
3.1 Transcription factors and transcriptional regulation	49	(4)
3.2 Chromatin structure	53	(1)
3.3 Epigenetic regulation of transcription	54	(3)
3.4 Evidence for a role of epigenetics in carcinogenesis	57	(3)
3.5 Telomeres and telomerase	60	(3)
3.6 Epigenomic and histonomic drugs	63	(1)
3.7 Telomerase inhibitors	64	(5)
4 Growth factor signaling and oncogenes	69	(24)
4.1 Epidermal growth factor signaling: an important paradigm	69	(8)
4.2 Oncogenes	77	(8)
4.3 Kinase inhibitors	85	(4)
4.4 RAS-directed therapies	89	(4)
5 Growth inhibition and tumor suppressor genes	93	(26)
5.1 The retinoblastoma gene and protein	97	(4)
5.2 Mutations in the RB pathway and cancer	101	(1)
5.3 The p53 pathway	101	(8)
5.4 Mutations in the p53 pathway and cancer	109	(1)
5.5 Interaction of DNA viral protein products with Rb and p53	110	(2)
5.6 Cyclin dependent kinase inhibitors	112	(1)
5.7 Targeting of the p53 pathway	113	(6)
6 Apoptosis	119	(18)
6.1 Molecular mechanisms of apoptosis	119	(6)
6.2 Apoptosis and cancer	125	(4)
6.3 Apoptosis and chemotherapy	129	(2)
6.4 Apoptotic drugs	131	(6)
7 Stem cells and differentiation	137	(20)
7.1 Stem cells and cancer	138	(9)
7.2 Role of lineage-specific transcription factors in blocked differentiation	147	(4)
7.3 Inhibitors of the Wnt pathway	151	(1)
7.4 Inhibitors of the Hh pathway	152	(1)
7.5 Leukemia and differentiation therapies	153	(4)
8 Metastasis	157	(24)
8.1 Steps of metastasis	158	(1)
8.2 Tools of cell migration: cell adhesion molecules, integrins, and proteases	159	(2)
8.3 Intravasation	161	(2)
8.4 Transport	163	(1)
8.5 Extravasation	163	(1)
8.6 Metastatic colonization	164	(1)
8.7 The angiogenic switch	165	(5)
8.8 Other means of tumor neovascularization	170	(2)
8.9 Metalloproteinase inhibitors (MP's)	172	(1)
8.10 Antiangiogenic therapy and vascular targeting	172	(9)
9 Nutrients, hormones, and gene interactions	181	(20)
9.1 Causative factors	183	(3)
9.2 Preventative factors	186	(5)
9.3 Genetic polymorphisms and diet	191	(1)
9.4 Vitamin D: a link between nutrients and hormone action	192	(1)
9.5 Hormones and cancer	193	(3)
9.6 'Enhanced' foods	196	(1)
9.7 Drugs that target estrogen	196	(5)
10 Cancer in the future: focus on diagnostics and immunotherapy	201	(22)
10.1 Cancer vaccines	202	(7)
10.2 Microarrays and expression profiling	209	(2)
10.3 Molecular diagnostics and prognostics	211	(3)
10.4 Cancer research bioinformatics	214	(1)
10.5 Improved clinical trial design	214	(2)
10.6 Treating cancer symptoms	216	(1)
10.7 A career in cancer research: the people, agencies, and process involved in drug development	216	(2)
10.8 Are we making progress?	218	(5)
APPENDIX 1: CELL CYCLE REGULATION	223	(2)
APPENDIX 2: CENTERS FOR CANCER RESEARCH	225	(4)
GLOSSARY	229	(8)
INDEX	237