Chapter category: Cell Cycle
p53, Apoptosis, and Cancer Therapy
Cell Cycle Checkpoints and Cancer
Edited by: Mikhail V. BlagosklonnyISBN: 1-58706-067-1
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Chapter authors:
Rosandra Kaplan and David E. Fisher
Several decades of genetic and molecular study have revealed enormous insights into the mechanistic underpinnings of cancer. From the identification of dominantly acting oncogenes to the signaling pathways which modulate the cell cycle, our understanding of the machinery of cell cycle progression as well as the regulatory circuits which control it have never been so detailed. However the translation of these discoveries into improved therapeutic approaches has been slow. The more recent appreciation of the pivotal role for cell survival pathways in both the genesis of malignancies as well as their response to treatment has created a burst of excitement for the prospect that the unraveling of these pathways stands to more directly impact on therapeutic strategies for cancer. This chapter focuses on one major regulator of cell survival in human cancer: the p53 tumor suppressor gene product. Abundant evidence suggests that the action(s) of this one gene serves to prevent formation of many human malignancies and likely mediates the successful treatment responses in those few tumors in which current/traditional chemotherapy produces durable cures. Through the study of p53’s central roles in the cancer cell, molecular oncology has become inextricably linked to the quest for novel approaches to the therapy of cancer.
Additional chapters from this book:
Autocrine Transformation: Cytokine Model
James A. McCubrey, Xiao-yang Wang, Paul A. Algate, William L. Blalock and Linda S. Steelman
Autocrine growth factor secretion by cells is a frequent event involved in malignant transformation. Constitutive growth factor gene expression can in turn result in the deregulation of survival. ...
Cell Cycle Molecular Targets and Drug Discovery
John Boulamwini
There have emerged, within the aberrant cell cycle regulatory pathways frequently encountered in cancer cells, several potential targets for novel anticancer drug discovery. Cyclin-dependent k...
Small Molecule Inhibitors of Cyclin-Dependent Kinases
Geoffrey I. Shapiro
Cyclin-dependent kinases (cdks) are core components of the cell cycle machinery. Orderly transition between cell cycle phases requires the scheduled activity of the cdks, governed in part by their...
Non-Apoptotic Responses to Anticancer Agents: Mitotic Catastrophe, Senescence, and the Role of p53 and p21
Igor B. Roninson, Bey-Dih Chang, Eugenia V. Broude
Chemotherapeutic drugs and radiation inhibit tumor cell proliferation by inducing growth arrest and cell death. The best-studied antiproliferative response to anticancer agents is programmed cell ...
p53, Apoptosis, and Cancer Therapy
Rosandra Kaplan and David E. Fisher
Several decades of genetic and molecular study have revealed enormous insights into the mechanistic underpinnings of cancer. From the identification of dominantly acting oncogenes to the signaling...
G2 Checkpoint and Anticancer Therapy
Zoe A. Stewart and Jennifer A. Pietenpol
Over the past two decades, the basic molecular events controlling eukaryotic G2 to M-phase cell cycle transition have been deciphered. Studies in a variety of organisms have identified an evol...
Hypoxia and Cell Cycle
Rachel A. Freiberg, Susannah L. Green and Amato J. Giaccia
Tumor initiation is dependent on several key changes in the requirements for cell growth. Three of the most important features that distinguish transformed cells from untransformed cells are the l...
Functional Interactions Between BRCA1 and the Cell Cycle
Timothy K. MacLachlan and Wafik El-Deiry
The onset of breast cancer in women is one of the most devastating diseases known today, afflicting approximately one in nine women in Western countries. In families that inherit breast and ovaria...
The Regulation of p53 Growth Suppression
Ronit Vogt Sionov, Igal Louria Hayon, Ygal Haupt
The p53 tumor suppressor protein plays a pivotal role in the cellular response to stress. A variety of stress signals trigger accumulation and activation of p53 to halt the cell cycle and to preve...
DNA Damage, Cell Cycle Control, and Cancer
Jens Oliver, Temesgen Samuel and H. Oliver Weber
Cell cycle checkpoints constitute a network of signal transduction mechanisms to monitor DNA damage and regulate progression through the cell cycle. A series of events is triggered in cells upon DNA d...
The Restriction Point of the Cell Cycle
Mikhail V. Blagosklonny and Arthur B. Pardee
TGrowth factors (GF) initiate and maintain transition through G1 to S phase. GF-dependence ends with phosphorylation of Rb by cyclin-dependent kinases (CDKs), enabling cells to pass through th...
Signal Transduction Pathways: Cytokine Model
J. A. McCubrey, William L. Blalock, Fumin Chang,
Growth factors (GF) initiate and maintain transition through G1 to S phase. GF-dependence ends with phosphorylation of Rb by cyclin-dependent kinases (CDKs), enabling cells to pass through the...
