Apoptosis and Cancer Chemotherapy (Cancer Drug Discovery and Development)

The past few years have witnessed an astonishing international effort that established the role of some 20 new molecules in apoptosis and added activation or suppression of apoptosis to the accepted biological functions of a great many others already familiar in cancer biology. Some of these molecules are receptors, transducing cytokine-mediated signals; others appear to intensify or diminish the risk that a compro­ mised cell will fire its apoptosis effector mechanism. All are of interest as potential targets for tumor therapy, and some may prove to be control points influenced in the pathogenesis of cancer and other diseases as diverse as viral infection, neurodegenerative disorders, and stroke. Sometimes, in the midst of these developments, a kind of euphoria ap­ pears to have gripped the research community, with the expectation that apoptosis will afford explanations to many unsolved questions in cellu­ lar regulation. This book, in a series of thoughtful and provocative ar­ ticles--some from established leaders in the field, and others from younger scientists--seeks to redress the balance.

this Collection Of Thoughtful And Provocative Articles Focused On The Key Issues In Apoptosis, Ranges From The Role Of Apoptosis In Defining The Response Of Authentic Tumor Populations To Chemotherapeutic Agents To The Mechanisms Coupling Dna Damage To The Activation Pathway Of Apoptosis. It Reviews The Profusion Of New Signaling, Modulating, And Effector Molecules Now Implicated In Apoptosis And Whether Other Routes To Programmed Cell Death May Exist. Also Addressed Are The Nature Of The Molecules That Will Either Constitute Targets For Future Drugs Or Influence The Efficacy Of Current Therapies, As Well As Mechanistic Questions On The Control Of Apoptosis. By Focusing On Essential Questions And Critically Summarizing The Overwhelming Tide Of Recent Research Results, Apoptosis And Cancer Chemotherapy Illuminates Not Only The Potential Targets For Tumor Therapy, But Beyond That, Potential Control Points For Cancer And Such Diverse Diseases As Viral Infection, Neurodegenerative Disorders, And Stroke. This Collection Of Cutting-edge Reviews By Established Leaders In The Field Critically Summarizes The Recent Discoveries Concerning Apoptosis, Cell Suicide. The Book Looks Forward To The Time When Such Cell Death Can Be Controlled To Treat Cancer And A Host Of Other Diseases As Diverse As Viral Infection, Neurodegenerative Disorders, And Stroke.

the Book Contains Black-and-white Illustrations.

the Realization That Responses Of Tumors To Chemotherapy Also Depends On So-called “downstream” Events Has Created Much Interest In Regulators Of Apoptosis As Determinants Of Drug Action. And, Because These Regulators Also Play Key Roles In Multistage Carcinogenesis, They Provide Important Potential Targets For New Therapies. Acknowledged Leaders In The Field Have Written Thoughtful And Up-to-date Reviews, As Well As Personal Views Of Some Of The Conundrums Facing The Field, Such As Finding The Prognostic Value Of Molecules Like P53 And Bcl-2 In Determining Responses To Therapies And How These Molecules Function In Different Cellular Contexts. This Series Of Short Reviews, With Prioritized Reading Recommendations, Presents A Contemplative Assessment Of The Field.

This collection of thoughtful and provocative articles focused on the key issues in apoptosis, ranges from the role of apoptosis in defining the response of authentic tumor populations to chemotherapeutic agents to the mechanisms coupling DNA damage to the activation pathway of apoptosis. It reviews the profusion of new signaling, modulating, and effector molecules now implicated in apoptosis and whether other routes to "programmed" cell death may exist. Also addressed are the nature of the molecules that will either constitute targets for future drugs or influence the efficacy of current therapies, as well as mechanistic questions on the control of apoptosis. By focusing on essential questions and critically summarizing the overwhelming tide of recent research results, Apoptosis and Cancer Chemotherapy illuminates not only the potential targets for tumor therapy, but beyond that, potential control points for cancer and such diverse diseases as viral infection, neurodegenerative disorders, and stroke. This collection of cutting-edge reviews by established leaders in the field critically summarizes the recent discoveries concerning apoptosis, cell suicide. The book looks forward to the time when such cell death can be controlled to treat cancer and a host of other diseases as diverse as viral infection, neurodegenerative disorders, and stroke.

Booknews

Twenty-one reviews provide a balanced assessment of recent discoveries that serves as a foundation for further research. Topics include the role of p53 in chemosensitivity; involvement of c-Abl tyrosine kinase in apoptotic response to anticancer agents; The role of Bax in development and oncogenesis; insulin-like growth factor-1 receptor as a target for anticancer therapy; molecular regulation and therapeutic implications of cell death in prostate cancer; and apoptosis and breast cancer. Concluding remarks ask whether the information explosion on apoptosis has affected clinical practice. Annotation c. Book News, Inc., Portland, OR (booknews.com)

Front Matter....Pages i-xv Does Apoptosis Contribute to Tumor Cell Sensitivity to Anticancer Agents?....Pages 1-19 p53, Apoptosis, and Chemosensitivity....Pages 21-36 The Role of p53 in Chemosensitivity....Pages 37-52 Function of the p53 Gene Family....Pages 53-68 Mismatch Repair Deficiency, Apoptosis, and Drug Resistance....Pages 69-85 Involvement of c-Abl Tyrosine Kinase in Apoptotic Response to Anticancer Agents....Pages 87-98 Bcl-2 Family Proteins....Pages 99-116 Bax, a Death Effector Molecule....Pages 117-128 Bax, a Proapoptotic Protein Forming Channels in Mitochondria....Pages 129-141 Mechanism of Action of the Proapoptotic Gene Bak ....Pages 143-156 Killers or Clean-Up Crew....Pages 157-174 Role of CD95 (APO-1/Fas) System in Chemotherapy....Pages 175-187 Insulin-Like Growth Factor-1 Receptor as a Target for Anticancer Therapy....Pages 189-203 Drug Resistance and the Survival Niche....Pages 205-221 Chemotherapy, Tumor Microenvironment, and Apoptosis....Pages 223-240 Molecular Regulation and Therapeutic Implications of Cell Death in Prostate Cancer....Pages 241-255 Chemotherapy and Apoptosis in the Ovary....Pages 257-273 Role of Bcl-2 Family Members in Homeostasis, in Toxicology in Normal Intestine, and for Prognosis of Colonic Carcinomas....Pages 275-290 Apoptosis and Breast Cancer....Pages 291-303 Role of Apoptosis in Human Neuroblastomas....Pages 305-318 Response of Testicular Tumors to Chemotherapy....Pages 319-329 Concluding Remarks....Pages 331-332 Back Matter....Pages 333-342