Head and Neck Cancer: Basic and Clinical Aspects (Cancer Treatment and Research, 74)

Over the last 50 years, drug development and clinical trials have resulted in successful complete responses in diseases such as childhood leukemia, testicular cancer and Hodgkin's disease. We are still, however, confronted with over 500,000 cancer-related deaths per year. Clearly, the phenomenon of drug resistance is largely responsible for these failures and continues to be an area of active investigation. Since the last volume in this series, we have learned that the energy-dependent drug efflux protein, p-glycoprotein, encoded by the MDR 1 gene, is a member of a family of structurally related transport polypeptides, thus allowing us to explore the relationship between structure and function. In addition to ongoing well designed clinical trials aimed at reversing MDR mediated drug resistance, the first gene therapy studies with the MDR 1 gene retrovirally transduced into human bone marrow cells are about to be initiated. Although MDR is currently the most understood mechanism of drug resistance, we are uncovering increasing knowledge of alternative molecular and biochemical mechanisms of drug resistance to antimetabolites, cisplatin and alkylating agents and developing new strategies for circumventing such resistance. It is clear that drug resistance is complex, and many mechanisms exist by which cancer cells may overcome the cytotoxicity of our known chemotherapeutic agents. As our understanding of each of these mechanisms expands, well designed models will be necessary to test laboratory hypotheses and determine their relationship to drug resistance in humans. It is this integration of basic science and clinical investigation that will both advance our scientific knowledge and result in the improvement of cancer therapy.

Over the last 50 years, drug development and clinical trials have resulted in successful complete responses in diseases such as childhood leukemia, testicular cancer and Hodgkin's disease. We are still, however, confronted with over 500,000 cancer-related deaths per year. Clearly, the phenomenon of drug resistance is largely responsible for these failures and continues to be an area of active investigation.
Since the last volume in this series, we have learned that the energy-dependent drug efflux protein, p-glycoprotein, encoded by the MDR 1 gene, is a member of a family of structurally related transport polypeptides, thus allowing us to explore the relationship between structure and function. In addition to ongoing well designed clinical trials aimed at reversing MDR mediated drug resistance, the first gene therapy studies with the MDR 1 gene retrovirally transduced into human bone marrow cells are about to be initiated.
Although MDR is currently the most understood mechanism of drug resistance, we are uncovering increasing knowledge of alternative molecular and biochemical mechanisms of drug resistance to antimetabolites, cisplatin and alkylating agents and developing new strategies for circumventing such resistance.
It is clear that drug resistance is complex, and many mechanisms exist by which cancer cells may overcome the cytotoxicity of our known chemotherapeutic agents. As our understanding of each of these mechanisms expands, well designed models will be necessary to test laboratory hypotheses and determine their relationship to drug resistance in humans. It is this integration of basic science and clinical investigation that will both advance our scientific knowledge and result in the improvement of cancer therapy.

Throughout the world, head and neck cancer is a major threat to public health and a significant challenge to both clinicians and basic scientists. Despite extensive efforts in primary prevention, screening, early detection, and therapy, long-term survival rates have not improved substantially in the last three decades. This book covers a wide range of exciting new findings in both clinical and basic sciences as they are relevant to head and neck cancer. These findings have recently enhanced our understanding of head and neck carcinogenesis at the genetic and molecular levels, offering the promise of improved preventive and therapeutic strategies. This book will also present information on the important clinical advances that have been made in chemoprevention, organ preservation, and the simultaneous use of chemo­ therapy and radiotherapy. The first part provides an overview of the etiology and biology of head and neck cancer, including an examination of human papillomaviruses in both benign and malignant lesions. This section also discusses the carcinogenic process at the genetic and molecular levels, as well as aberrant squamous differentiation; increased understanding of these areas has great potential to translate into new strategies for cancer prevention. The second part describes recent advances in developing a risk model for head and neck cancer, as well as the application of genetic susceptibility data in chemoprevention. This section also includes overviews of the status of chemoprevention trials and of the process of invasion and metastasis in head and neck cancer. Clinical trials have two purposes -- to treat the patients in the trial, and to obtain information which increases our understanding of the disease and especially how patients respond to treatment. Statistical design provides a means to achieve both these aims, while statistical data analysis provides methods for extracting useful information from the trial data. Recent advances in statistical computing have enabled statisticians to implement very rapidly a broad array of methods which previously were either impractical or impossible. Biostatisticians are now able to provide much greater support to medical researchers working in both clinical and laboratory settings. As our collective toolkit of techniques for analyzing data has grown, it has become increasingly difficult for biostatisticians to keep up with all the developments in our own field. Recent Advances in Clinical Trial Design and Analysis brings together biostatisticians doing cutting-edge research and explains some of the more recent developments in biostatistics to clinicians and scientists who work in clinical trials. Edited By Waun Ki Hong, Randal S. Weber. Includes Bibliographical References And Index. The human papillomaviruses (HPVs) are a large family of related DNA viruses. Edited By Peter F. Thall. Includes Bibliographical References And Index.