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Promises and Challenges of Oncology and Hematology, Including Geriatric Oncology
Critical Reviews in Oncology/Hematology 50 (2004) 1–2
Editorial for Volume 50
Promises and Challenges of Oncology and Hematology, Including Geriatric Oncology
The editors of Critical Reviews in Oncology Hematology (CROH) are pleased to share their thoughts in this editorial celebrating the 50th volume of this Journal. Recognized as an important review journal with an impact factor of 2.758, and now also incorporating original papers in Geriatric Oncology, CROH will evolve as times change. But its fundamentals are based on evidence, in all fields of oncology, and were pioneered by Stephen Davis, our much regretted colleague who had given its prominence to the journal. The spheres of morality, deontology, law and clinical practice often overlap. As a consequence, there is no precise definition of the ethics domain in medicine and in oncology. Our goal has been to address specific issues that pose a real challenge to practicing oncologists. We have chosen articles dealing with “practical reason” and we have tried to be creative and unconventional, aiming for a balance between asking moot questions and providing practical guidelines. We hope to have developed an effective strategy to bring ethics to our readership, in a way that acknowledges that medicine is primarily a praxis to be shared by physicians, nurses, caregivers, patients and all society. The past 25 years have brought more knowledge on cancer than the previous 25 centuries. The progresses that have been made in cancer biology have completely changed the aims and approaches of research in oncology. The discovery of oncogenes and of tumor suppressor genes, the identification of the mechanisms of cell proliferation and of cell death, the understanding of the invasive and metastatic processes are the successive milestones that have been raised on this highway. In parallel, genome sequencing offers a comprehensive picture of the genetic information underlying all biological phenomena. As a result, we now have an integrated view of oncogenesis and we are able to map the alterations encountered in cancer cells both at the level of the complex signal transduction cascades and at the level of the genes encoding every protein involved in the cancer process. The understanding that cell proliferation was only a consequence of multiple genetic alterations in cancer has shifted the quest for drug targets from the effect to the cause; there is now a proliferation of potential targets for anticancer drug design, with already several “smart drugs” on the market, some significantly improving the survival and the quality of 1040-8428/$ – see front matter © 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.critrevonc.2004.03.001
life of selected patients receiving these new therapies. The design of trials of classic cytotoxics and novel agents targeting tyrosine kinases, proteases, antiangiogenetic agents, antisense inhibitors, and monoclonal antibodies is undergoing drastic changes. It is no longer acceptable to compare drug A versus drug B in a huge clinical trial without exploring why drug A can be superior to drug B, why some patients will respond and why other will not. Registration trials in the future will most likely target molecular characteristics of cancers rather than the site of tumor origin. Clinical research and experimental oncology should no longer be considered as different approaches, but as two faces of the same approach. The basic cancer scientist should understand that he or she is committed to the progress of cancer treatment in humans, and the practicing oncologist should admit that he or she has to take cancer biology in consideration in order to prescribe the best available therapy. But many challenges face the oncologist in clinical research. Most studies are performed in patients with advanced disease. How can we best define the population who will benefit from novel targeted therapies? What is the cost-benefit ratio of developing innovative drugs that may only work in a small subset of patients? Which novel agents would be best utilized over long periods of time in the adjuvant setting? Efforts in the individualization and validation of predictive factors should be intensified, in order to minimize the risk of exposure of patients to inappropriate drugs. But will the costs outweigh the risks and decrease chronic illness, suffering and hospitalization costs? We all know that cancer is a curable disease in mice: the question is whether humans should evolve to mice or whether researchers should place their major efforts on human cancer! Hematopoiesis, the production of blood cells, is an example of fundamental mechanisms whose study can lead to improvements in therapy. Hematopoiesis involves interactions between hematopoietic stem and progenitor cells, cytokines and chemokines that influence the production, survival, self-renewal, differentiation and migration/homing of the stem/progenitor cells, and the stromal and accessory cells that produce the cytokines and chemokines. Key issues in hematopoiesis include a better understanding of specific stem cell functional characteristics. Such charac-
2
Editorial for Volume 50
teristics include the cytokines and stromal/accessory cells that play a role in self-renewal of stem cells, as well as in the homing of these cells to the bone marrow for enhanced engraftment, and the mobilization of these cells from the bone marrow to the blood where they can be collected for transplantation. How self-renewal and homing/mobilization of stem cells, and other stem cell characteristics such as survival and differentiation are mediated at an intracellular level, including genomics and proteomics, should enhance our ability to better utilize stem cells and understand how abnormalities during leukemia are manifest and might be controlled. Studies on differentiation of embryonic stem cells towards the hematopoietic lineage may help shed light on many of the above areas of investigation, especially hematopoietic stem cell self-renewal. Critical Reviews in Oncology Hematology promotes the study of Geriatric Oncology, recognizing that the majority of patients dying from cancer are in that age group, where minimal research has been conducted until recently. The ability of the medical care system, including preventive medicine, control of cardiovascular risks (strokes, heart attacks, etc) and other public health measures has enabled many nations to witness a significant increase in the median age of males and females that is rapidly approaching 80 years of age. The elderly represent 15% of the population in Europe but use a large proportion of health benefits provided in their countries. This poses major challenges to society, and decisions should be made on appropriate evidence. Moreover, one has to know that the majority of elderly patients with cancer are actually in countries with limited resources but huge populations. We, therefore, must be prepared to provide education and research (both biologic and clinical) to examine the complex issues of risk for
neoplasm, research into causation, reasons for reluctance to carry out screening and referral for consideration of treatment options in the elderly population as well as specific programs of care for this important group of patients. Modifications of the Comprehensive Geriatric Assessment Tool are under investigation at the present time and will help considerably to assess which patients are suitable for specific interventions. In the United States there is an emphasis on developing and implementing formal training programs in the medical subspecialties that will result in a “fusion” product between the specialties of interest (for example: Medical Oncology and Geriatrics). These considerations explain why CROH has positioned itself to be in the forefront of journals that will provide a continual forum for these important issues. M. Aapro Editor-in-Chief J. Bennett Cancer of the Elderly, North America H. Broxmeyer Hematology L. Repetto Cancer of the Elderly, Europe and other J. Robert Experimental Oncology C. Sternberg Solid Tumors A. Surbone Medical Ethics
Editorial for Volume 50
Promises and Challenges of Oncology and Hematology, Including Geriatric Oncology
The editors of Critical Reviews in Oncology Hematology (CROH) are pleased to share their thoughts in this editorial celebrating the 50th volume of this Journal. Recognized as an important review journal with an impact factor of 2.758, and now also incorporating original papers in Geriatric Oncology, CROH will evolve as times change. But its fundamentals are based on evidence, in all fields of oncology, and were pioneered by Stephen Davis, our much regretted colleague who had given its prominence to the journal. The spheres of morality, deontology, law and clinical practice often overlap. As a consequence, there is no precise definition of the ethics domain in medicine and in oncology. Our goal has been to address specific issues that pose a real challenge to practicing oncologists. We have chosen articles dealing with “practical reason” and we have tried to be creative and unconventional, aiming for a balance between asking moot questions and providing practical guidelines. We hope to have developed an effective strategy to bring ethics to our readership, in a way that acknowledges that medicine is primarily a praxis to be shared by physicians, nurses, caregivers, patients and all society. The past 25 years have brought more knowledge on cancer than the previous 25 centuries. The progresses that have been made in cancer biology have completely changed the aims and approaches of research in oncology. The discovery of oncogenes and of tumor suppressor genes, the identification of the mechanisms of cell proliferation and of cell death, the understanding of the invasive and metastatic processes are the successive milestones that have been raised on this highway. In parallel, genome sequencing offers a comprehensive picture of the genetic information underlying all biological phenomena. As a result, we now have an integrated view of oncogenesis and we are able to map the alterations encountered in cancer cells both at the level of the complex signal transduction cascades and at the level of the genes encoding every protein involved in the cancer process. The understanding that cell proliferation was only a consequence of multiple genetic alterations in cancer has shifted the quest for drug targets from the effect to the cause; there is now a proliferation of potential targets for anticancer drug design, with already several “smart drugs” on the market, some significantly improving the survival and the quality of 1040-8428/$ – see front matter © 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.critrevonc.2004.03.001
life of selected patients receiving these new therapies. The design of trials of classic cytotoxics and novel agents targeting tyrosine kinases, proteases, antiangiogenetic agents, antisense inhibitors, and monoclonal antibodies is undergoing drastic changes. It is no longer acceptable to compare drug A versus drug B in a huge clinical trial without exploring why drug A can be superior to drug B, why some patients will respond and why other will not. Registration trials in the future will most likely target molecular characteristics of cancers rather than the site of tumor origin. Clinical research and experimental oncology should no longer be considered as different approaches, but as two faces of the same approach. The basic cancer scientist should understand that he or she is committed to the progress of cancer treatment in humans, and the practicing oncologist should admit that he or she has to take cancer biology in consideration in order to prescribe the best available therapy. But many challenges face the oncologist in clinical research. Most studies are performed in patients with advanced disease. How can we best define the population who will benefit from novel targeted therapies? What is the cost-benefit ratio of developing innovative drugs that may only work in a small subset of patients? Which novel agents would be best utilized over long periods of time in the adjuvant setting? Efforts in the individualization and validation of predictive factors should be intensified, in order to minimize the risk of exposure of patients to inappropriate drugs. But will the costs outweigh the risks and decrease chronic illness, suffering and hospitalization costs? We all know that cancer is a curable disease in mice: the question is whether humans should evolve to mice or whether researchers should place their major efforts on human cancer! Hematopoiesis, the production of blood cells, is an example of fundamental mechanisms whose study can lead to improvements in therapy. Hematopoiesis involves interactions between hematopoietic stem and progenitor cells, cytokines and chemokines that influence the production, survival, self-renewal, differentiation and migration/homing of the stem/progenitor cells, and the stromal and accessory cells that produce the cytokines and chemokines. Key issues in hematopoiesis include a better understanding of specific stem cell functional characteristics. Such charac-
2
Editorial for Volume 50
teristics include the cytokines and stromal/accessory cells that play a role in self-renewal of stem cells, as well as in the homing of these cells to the bone marrow for enhanced engraftment, and the mobilization of these cells from the bone marrow to the blood where they can be collected for transplantation. How self-renewal and homing/mobilization of stem cells, and other stem cell characteristics such as survival and differentiation are mediated at an intracellular level, including genomics and proteomics, should enhance our ability to better utilize stem cells and understand how abnormalities during leukemia are manifest and might be controlled. Studies on differentiation of embryonic stem cells towards the hematopoietic lineage may help shed light on many of the above areas of investigation, especially hematopoietic stem cell self-renewal. Critical Reviews in Oncology Hematology promotes the study of Geriatric Oncology, recognizing that the majority of patients dying from cancer are in that age group, where minimal research has been conducted until recently. The ability of the medical care system, including preventive medicine, control of cardiovascular risks (strokes, heart attacks, etc) and other public health measures has enabled many nations to witness a significant increase in the median age of males and females that is rapidly approaching 80 years of age. The elderly represent 15% of the population in Europe but use a large proportion of health benefits provided in their countries. This poses major challenges to society, and decisions should be made on appropriate evidence. Moreover, one has to know that the majority of elderly patients with cancer are actually in countries with limited resources but huge populations. We, therefore, must be prepared to provide education and research (both biologic and clinical) to examine the complex issues of risk for
neoplasm, research into causation, reasons for reluctance to carry out screening and referral for consideration of treatment options in the elderly population as well as specific programs of care for this important group of patients. Modifications of the Comprehensive Geriatric Assessment Tool are under investigation at the present time and will help considerably to assess which patients are suitable for specific interventions. In the United States there is an emphasis on developing and implementing formal training programs in the medical subspecialties that will result in a “fusion” product between the specialties of interest (for example: Medical Oncology and Geriatrics). These considerations explain why CROH has positioned itself to be in the forefront of journals that will provide a continual forum for these important issues. M. Aapro Editor-in-Chief J. Bennett Cancer of the Elderly, North America H. Broxmeyer Hematology L. Repetto Cancer of the Elderly, Europe and other J. Robert Experimental Oncology C. Sternberg Solid Tumors A. Surbone Medical Ethics