There is no question that loss of cell cycle checkpoint regulation is an intrinsic characteristic of cancer. However, many tumors retain parallel checkpoint pathways that are activated by antitumor agents and facilitate therapeutic response. Failures in these therapy-linked checkpoint controls are closely associated with cancers that are highly resistant to therapeutic interventions. Checkpoint Controls and Targets in Cancer provides present-day mechanistic understandings of how multiple sets of proteins orchestrate cell cycle progression, discusses critical checkpoint controls that are evaded for cancer development, focuses on checkpoint pathways associated with antitumor effects, and identifies specific checkpoint regulators for targeting with small molecules in the clinical management of cancer. These aspects of cell cycle checkpoints are articulated critically by renowned experts from both academia and industry, and new concepts are forwarded that challenge existing dogmas. Collectively, Checkpoint Controls and Targets in Cancer provides a unique collection of insightful contributions, which are timely and offer significant interest and appeal to basic, translational and clinical scientists.
Author(s): Krijn K. Dijkstra, Cristophe Blanchetot, Johannes Boonstra (auth.), Zahid H. Siddik (eds.)
Series: Cancer Drug Discovery and Development
Edition: 1
Publisher: Humana Press
Year: 2009
Language: English
Pages: 274
Tags: Cancer Research; Oncology; Pharmacology/Toxicology
Front Matter....Pages i-xiv
Front Matter....Pages 1-1
Evasion of G1 Checkpoints in Cancer....Pages 3-26
Distinct Pathways Involved in S-Phase Checkpoint Control....Pages 27-36
Mechanisms of G2 Phase Arrest in DNA Damage-Induced Checkpoint Response....Pages 37-51
Centrosomes in Checkpoint Responses....Pages 53-67
Interplay of 14-3-3 Family of Proteins with DNA Damage-Regulated Molecules in Checkpoint Control....Pages 69-80
Front Matter....Pages 82-82
Chromatin Modifications and Orchestration of Checkpoint Response in Cancer....Pages 83-93
DNA Damage Response and the Balance Between Cell Survival and Cell Death....Pages 95-108
Dysfunction of the RB Retinoblastoma Gene in Cancer....Pages 109-122
G1 Phase Cyclins in Cancer Development and Progression....Pages 123-153
The BRCA1/2 Pathway Prevents Some Leukemias and Lymphomas in Addition to Breast/Ovarian Cancers: Malignancies that Overcome Checkpoint Controls....Pages 155-168
Front Matter....Pages 170-170
Regulation of p53 Activity and Associated Checkpoint Controls....Pages 171-188
The Importance of p53 Signaling in the Response of Cells to Checkpoint Inhibitors....Pages 189-198
Targeting p21-Dependent Pathways for Cell Death in Cancer Therapy....Pages 199-213
p27Kip1 as a Biomarker and Target for Treatment of Cancer....Pages 215-233
Targeting Cyclin-Dependent Kinases with Small Molecule Inhibitors....Pages 235-244
Chk1 and Chk2 as Checkpoint Targets....Pages 245-259
Targeting Cdc25 Phosphatases in Cancer Therapy....Pages 261-269
Back Matter....Pages 271-273
