- Email: [email protected]
Treating breast and prostate cancer
Forum
TRENDS in Molecular Medicine Vol.8 No.11 November 2002
543
Book Reviews
Nuclear war on cancer Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins edited by N.B. La Thangue and L.R. Bandara, Humana Press, 2002. $165.00 (hardback) (352 pages) ISBN 0-89603-938-2
The tremendous progress in identification of the molecular mechanisms of cancer has provided anticancer drug research with numerous potential targets. Most effort has been devoted to the targeting of oncogenic kinases. Indeed, inhibitors of the kinases, Bcr-Abl and FLK3, demonstrate excellent clinical and preclinical effectiveness. However, the effectiveness of these inhibitors is restricted to subgroups of leukemias and gastric cancers in which a sole oncogenic alteration drives leukogenesis and carcinogenesis. Most cancers acquire multiple genetic alterations in downstream signaling pathways, such as the Rb–E2F pathway and c-myc. This suggests that the transcription factors, E2F and c-myc, can be considered as anticancer drug targets, although the potential toxicity to normal cells is a concern. Another transcription factor that is a logical therapeutic target is hypoxia-inducible factor 1 (HIF-1), which is needed for cancer cells to survive hypoxia and to induce angiogenesis, and might also be required for metastasis. Hence, selective inhibition of HIF-1 might be a promising direction. In contrast to kinases, the use of transcription factors in anticancer drug development is still in its infancy. However, as emphasized by the editors of Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins, chance favors the prepared mind. Nicholas La Thangue and Lasantha Bandara are well known for their work on the interplay between E2F, p53 and c-myc, as well as p300 and histone deacetylases, and these studies are, perhaps, responsible for the choice of topics in this book. Topics http://tmm.trends.com
covered include the transcription factors that are most universally affected in cancer, such as E2F, activator protein 1 (AP-1), HIF-1 and c-myc, as well as histone acetyltranferases and histone deacetylases. Other interesting and informative chapters describe β-catenin, Mdm-2, breast-cancer-susceptibility proteins 1 and 2 (BRCA 1 and 2), human papillomaviruses, apoptin, steroid receptors, and also mitogen-activated and cyclin-activated kinases. E2F-1 and HIF-1 seem to be the central focus of the book, and many readers will agree that these factors are two of the central players in tumor development. Hence, E2F-1 and HIF-1 are discussed in two chapters each, from different perspectives. In his chapter, William Kaelin envisions two scenarios for targeting E2F: either with E2F antagonists to arrest the cell cycle, or with E2F agonists to induce apoptosis. This thoughtful analysis indicates that opposite approaches can be considered for clinical development, given that we understand the goal of therapeutic intervention. In another chapter, Debabrata Banerjee and Joseph Bertino describe in detail possible strategies for targeting E2F using decoy oligonucleotides, peptides and other approaches. This book provides a detailed account of our understanding of transcriptionfactor oncoproteins and tumor suppressors, and of the impact that this knowledge has on cancer drug discovery. The book should be of interest to a wide readership, especially scientists working in cancer drug development, despite the fact that several possible topics are not discussed. For example, although there is a chapter focusing on Mdm-2 and ARF, there is no separate chapter covering p53. However p53 as a cell-cycle-checkpoint protein has already been extensively reviewed in other books, such as Cell Cycle Checkpoints and Cancer [1]. I hope that these two books will complement each other. Mikhail V. Blagosklonny Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA. e-mail: [email protected] Reference 1 Blagosklonny, M.V., ed. (2002) Cell Cycle Checkpoints and Cancer, Landes Bioscience, Georgetown, TX, USA
Treating breast and prostate cancer Hormone Therapy in Breast and Prostate Cancer edited by V.C. Jordan and B.J.A. Furr. Humana Press, 2002. US$135.00 (436 pages) ISBN 0-896-03673-1
Hormone Therapy in Breast and Prostate Cancer offers an authoritative stateof-the-art account of the role of hormones in prostate and breast cancer. The book is divided into 18 chapters or sections, which cover most of our present knowledge regarding the endocrinology of these two important glands. The introductory chapter by the editors is well written and clearly establishes the pace of the following sections. In general, the book is well organized and easy to read. Most of the chapters depict pure laboratory work, whilst a few contain a more translational approach. Nonetheless, all of the chapters are extremely useful to both researchers and clinicians. Some of the chapters contain a superabundance of bibliographic citations that, in relation to their content, creates an imbalance in the architecture of the entire book. The same applies to the uneven quality of illustrations from one chapter to another. One constant problem is repetition from one chapter to another. For example, the same formulation is repeated more than once through the book. Nevertheless, allowing for these small deficiencies, the book is authoritative and up-to-date, and not only provides a significant insight into the history of the endocrine understanding of breast and prostate cancer, but also provides new data that will progress the field. Hormone Therapy in Breast and Prostate Cancer is a worthwhile addition to a well organized library that not only provides important information for the practicing physician
1471-4914/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
544
Forum
TRENDS in Molecular Medicine Vol.8 No.11 November 2002
but also for the researcher, and for those who wish to cross the edge of translational research. Jose Russo Breast Cancer Research Lab, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. e-mail: [email protected]
An early step in a long ascent Molecular Pathology of Type 1 Diabetes Mellitus edited by M.G. von Herrath, Karger, 2001. CHF 288.00/EUR 205.50/US$250.50 (X + 360 pages) ISBN 3-8055-7240-9
This book presupposes a sound general understanding of immunology. As a general pediatric endocrinologist with no particular background in immunology, I nevertheless found Molecular Pathology of Type I Diabetes Mellitus of interest as a reference volume, although it was often difficult to follow. For the clinical investigator, clinical or basic immunologist, or molecular biologist involved in the pathogenesis of type 1 diabetes mellitus (T1DM), the volume should serve as an up-to-date review of the complex and confounding field of the molecular basis of T1DM. Although general immunology is reviewed piecemeal throughout the volume, an introductory chapter reviewing the general principles of immunology would have strengthened the utility of this book for the non-immunologist considerably. In particular, because much of the volume considers experimental models of diabetes, a review of rodent immunology, its relationship to human immunology,
its terminology, and a glossary of terms to be used later in the book would have been invaluable. Without this, much of the terminology and many of the abbreviations in the book were difficult to follow for the uninitiated. In striving to bring together the wealth of research into the pathogenesis of T1DM, the chapters volley back and forth between the genetics and immunology of human T1DM and that of experimental models of T1DM. For the clinician, the chapters on the genetics of human T1DM, the role of the intestinal mucosa in determining the impact of environment on the condition, and the review of autoantibodies in human diabetes are particularly worthwhile. In these chapters, the interaction between genetics and environment is reviewed in the context of the theories of antigen mimicry, HLA predispositions, and thymic versus peripheral selection and regulation of T-cell recognition of self-antigens. Of necessity, most of the other chapters describe experimental models of diabetes such as the non-obese diabetic mouse and the BB rat. Within these chapters, the reader’s enthusiasm for enticing and provocative findings in experimental animals is often muffled by the admonition that what applies to rodent physiology and disease might not apply to human disease, with ample examples of where this has proved to be the case. There are several main themes that weave through the chapters of this book: the intriguing idea that early hygiene might determine susceptibility of a population to T1DM; the potential importance of the potency of self-antigen signal in determining thymic deletion or selection of a T-cell precursor; the importance of peripheral regulation of T cells that recognize self-antigens but have escaped deletion in the thymus;
and the role of cytokines in driving immune responses and pancreatic β-cell or T-cell apoptosis. The final chapter considers the holy grail of T1DM – immunotherapy and prevention – by reviewing some of the successes in decreasing the frequency or severity of diabetes in experimental models of T1DM (e.g. pretreatment with antigens and anti-CD3 antibodies). Clinical studies are underway in humans to test these same strategies for preventing T1DM. The book was published before release of the initial results of the Diabetes Prevention Trial 1 (DPT1) – the disappointing finding that subcutaneous and periodic intravenous insulin therapy to prediabetic, ‘at risk’, first-degree relatives of patients with T1DM does not prevent the development of the disease [1]. Perhaps immunotherapy with oral insulin, as is also being tested in a second arm of the DPT1, or humanized anti-CD3 antibody therapy will prove more promising. Reality, however, is probably reflected best in the concluding words of Ridgway and Fathman in one of the chapters: ‘We are likely decades away from a convincing integrated view of the pathological genetic and cellular response cascade that results in autoimmune diabetes.’ Without this understanding of pathogenesis, hope for successful prevention and immunotherapy of human T1DM remains slim. Thomas A. Wilson Dept of Pediatrics, State University of New York, Stony Brook, NY 11794, USA. e-mail: [email protected] Reference 1 Schhen, A.J. and Philips, J.C. (2001) Info-congress. Insulin therapy for preventing type 1 diabetes in high-risk relatives: negative results of the Diabetes Prevention Trial – Type 1. Revue Medical de Liege 56, 536–538
Voice your opinions! Trends in Molecular Medicine provides a unique platform for all those interested in the understanding of the molecular basis of disease. Would you like to respond to any of the issues raised in this month’s Trends in Molecular Medicine? Letters to the Editor can have a maximum length of 750 words and can include up to 10 references and one figure or table. If you are interested in contributing a letter, please contact the Editor ([email protected]). Please note that letters commenting on Trends in Molecular Medicine articles are always sent to the appropriate authors for review and to give them the opportunity to reply. Please note: submission does not guarantee publication.
http://tmm.trends.com
TRENDS in Molecular Medicine Vol.8 No.11 November 2002
543
Book Reviews
Nuclear war on cancer Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins edited by N.B. La Thangue and L.R. Bandara, Humana Press, 2002. $165.00 (hardback) (352 pages) ISBN 0-89603-938-2
The tremendous progress in identification of the molecular mechanisms of cancer has provided anticancer drug research with numerous potential targets. Most effort has been devoted to the targeting of oncogenic kinases. Indeed, inhibitors of the kinases, Bcr-Abl and FLK3, demonstrate excellent clinical and preclinical effectiveness. However, the effectiveness of these inhibitors is restricted to subgroups of leukemias and gastric cancers in which a sole oncogenic alteration drives leukogenesis and carcinogenesis. Most cancers acquire multiple genetic alterations in downstream signaling pathways, such as the Rb–E2F pathway and c-myc. This suggests that the transcription factors, E2F and c-myc, can be considered as anticancer drug targets, although the potential toxicity to normal cells is a concern. Another transcription factor that is a logical therapeutic target is hypoxia-inducible factor 1 (HIF-1), which is needed for cancer cells to survive hypoxia and to induce angiogenesis, and might also be required for metastasis. Hence, selective inhibition of HIF-1 might be a promising direction. In contrast to kinases, the use of transcription factors in anticancer drug development is still in its infancy. However, as emphasized by the editors of Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins, chance favors the prepared mind. Nicholas La Thangue and Lasantha Bandara are well known for their work on the interplay between E2F, p53 and c-myc, as well as p300 and histone deacetylases, and these studies are, perhaps, responsible for the choice of topics in this book. Topics http://tmm.trends.com
covered include the transcription factors that are most universally affected in cancer, such as E2F, activator protein 1 (AP-1), HIF-1 and c-myc, as well as histone acetyltranferases and histone deacetylases. Other interesting and informative chapters describe β-catenin, Mdm-2, breast-cancer-susceptibility proteins 1 and 2 (BRCA 1 and 2), human papillomaviruses, apoptin, steroid receptors, and also mitogen-activated and cyclin-activated kinases. E2F-1 and HIF-1 seem to be the central focus of the book, and many readers will agree that these factors are two of the central players in tumor development. Hence, E2F-1 and HIF-1 are discussed in two chapters each, from different perspectives. In his chapter, William Kaelin envisions two scenarios for targeting E2F: either with E2F antagonists to arrest the cell cycle, or with E2F agonists to induce apoptosis. This thoughtful analysis indicates that opposite approaches can be considered for clinical development, given that we understand the goal of therapeutic intervention. In another chapter, Debabrata Banerjee and Joseph Bertino describe in detail possible strategies for targeting E2F using decoy oligonucleotides, peptides and other approaches. This book provides a detailed account of our understanding of transcriptionfactor oncoproteins and tumor suppressors, and of the impact that this knowledge has on cancer drug discovery. The book should be of interest to a wide readership, especially scientists working in cancer drug development, despite the fact that several possible topics are not discussed. For example, although there is a chapter focusing on Mdm-2 and ARF, there is no separate chapter covering p53. However p53 as a cell-cycle-checkpoint protein has already been extensively reviewed in other books, such as Cell Cycle Checkpoints and Cancer [1]. I hope that these two books will complement each other. Mikhail V. Blagosklonny Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA. e-mail: [email protected] Reference 1 Blagosklonny, M.V., ed. (2002) Cell Cycle Checkpoints and Cancer, Landes Bioscience, Georgetown, TX, USA
Treating breast and prostate cancer Hormone Therapy in Breast and Prostate Cancer edited by V.C. Jordan and B.J.A. Furr. Humana Press, 2002. US$135.00 (436 pages) ISBN 0-896-03673-1
Hormone Therapy in Breast and Prostate Cancer offers an authoritative stateof-the-art account of the role of hormones in prostate and breast cancer. The book is divided into 18 chapters or sections, which cover most of our present knowledge regarding the endocrinology of these two important glands. The introductory chapter by the editors is well written and clearly establishes the pace of the following sections. In general, the book is well organized and easy to read. Most of the chapters depict pure laboratory work, whilst a few contain a more translational approach. Nonetheless, all of the chapters are extremely useful to both researchers and clinicians. Some of the chapters contain a superabundance of bibliographic citations that, in relation to their content, creates an imbalance in the architecture of the entire book. The same applies to the uneven quality of illustrations from one chapter to another. One constant problem is repetition from one chapter to another. For example, the same formulation is repeated more than once through the book. Nevertheless, allowing for these small deficiencies, the book is authoritative and up-to-date, and not only provides a significant insight into the history of the endocrine understanding of breast and prostate cancer, but also provides new data that will progress the field. Hormone Therapy in Breast and Prostate Cancer is a worthwhile addition to a well organized library that not only provides important information for the practicing physician
1471-4914/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
544
Forum
TRENDS in Molecular Medicine Vol.8 No.11 November 2002
but also for the researcher, and for those who wish to cross the edge of translational research. Jose Russo Breast Cancer Research Lab, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. e-mail: [email protected]
An early step in a long ascent Molecular Pathology of Type 1 Diabetes Mellitus edited by M.G. von Herrath, Karger, 2001. CHF 288.00/EUR 205.50/US$250.50 (X + 360 pages) ISBN 3-8055-7240-9
This book presupposes a sound general understanding of immunology. As a general pediatric endocrinologist with no particular background in immunology, I nevertheless found Molecular Pathology of Type I Diabetes Mellitus of interest as a reference volume, although it was often difficult to follow. For the clinical investigator, clinical or basic immunologist, or molecular biologist involved in the pathogenesis of type 1 diabetes mellitus (T1DM), the volume should serve as an up-to-date review of the complex and confounding field of the molecular basis of T1DM. Although general immunology is reviewed piecemeal throughout the volume, an introductory chapter reviewing the general principles of immunology would have strengthened the utility of this book for the non-immunologist considerably. In particular, because much of the volume considers experimental models of diabetes, a review of rodent immunology, its relationship to human immunology,
its terminology, and a glossary of terms to be used later in the book would have been invaluable. Without this, much of the terminology and many of the abbreviations in the book were difficult to follow for the uninitiated. In striving to bring together the wealth of research into the pathogenesis of T1DM, the chapters volley back and forth between the genetics and immunology of human T1DM and that of experimental models of T1DM. For the clinician, the chapters on the genetics of human T1DM, the role of the intestinal mucosa in determining the impact of environment on the condition, and the review of autoantibodies in human diabetes are particularly worthwhile. In these chapters, the interaction between genetics and environment is reviewed in the context of the theories of antigen mimicry, HLA predispositions, and thymic versus peripheral selection and regulation of T-cell recognition of self-antigens. Of necessity, most of the other chapters describe experimental models of diabetes such as the non-obese diabetic mouse and the BB rat. Within these chapters, the reader’s enthusiasm for enticing and provocative findings in experimental animals is often muffled by the admonition that what applies to rodent physiology and disease might not apply to human disease, with ample examples of where this has proved to be the case. There are several main themes that weave through the chapters of this book: the intriguing idea that early hygiene might determine susceptibility of a population to T1DM; the potential importance of the potency of self-antigen signal in determining thymic deletion or selection of a T-cell precursor; the importance of peripheral regulation of T cells that recognize self-antigens but have escaped deletion in the thymus;
and the role of cytokines in driving immune responses and pancreatic β-cell or T-cell apoptosis. The final chapter considers the holy grail of T1DM – immunotherapy and prevention – by reviewing some of the successes in decreasing the frequency or severity of diabetes in experimental models of T1DM (e.g. pretreatment with antigens and anti-CD3 antibodies). Clinical studies are underway in humans to test these same strategies for preventing T1DM. The book was published before release of the initial results of the Diabetes Prevention Trial 1 (DPT1) – the disappointing finding that subcutaneous and periodic intravenous insulin therapy to prediabetic, ‘at risk’, first-degree relatives of patients with T1DM does not prevent the development of the disease [1]. Perhaps immunotherapy with oral insulin, as is also being tested in a second arm of the DPT1, or humanized anti-CD3 antibody therapy will prove more promising. Reality, however, is probably reflected best in the concluding words of Ridgway and Fathman in one of the chapters: ‘We are likely decades away from a convincing integrated view of the pathological genetic and cellular response cascade that results in autoimmune diabetes.’ Without this understanding of pathogenesis, hope for successful prevention and immunotherapy of human T1DM remains slim. Thomas A. Wilson Dept of Pediatrics, State University of New York, Stony Brook, NY 11794, USA. e-mail: [email protected] Reference 1 Schhen, A.J. and Philips, J.C. (2001) Info-congress. Insulin therapy for preventing type 1 diabetes in high-risk relatives: negative results of the Diabetes Prevention Trial – Type 1. Revue Medical de Liege 56, 536–538
Voice your opinions! Trends in Molecular Medicine provides a unique platform for all those interested in the understanding of the molecular basis of disease. Would you like to respond to any of the issues raised in this month’s Trends in Molecular Medicine? Letters to the Editor can have a maximum length of 750 words and can include up to 10 references and one figure or table. If you are interested in contributing a letter, please contact the Editor ([email protected]). Please note that letters commenting on Trends in Molecular Medicine articles are always sent to the appropriate authors for review and to give them the opportunity to reply. Please note: submission does not guarantee publication.
http://tmm.trends.com