Evolution Of The Molecular Biology Of Brain Tumors And The Therapeutic Implications

A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years. In particular recent new avenues regarding the role of stem cells and microRNAs along with further understanding of the importance of angiogenesis, immunotherapy and explanations for the resistance of the tumors to chemotherapeutic agents and radiation therapy has been developed. It is hopeful that this new information will lead to efficacious treatment strategies for these tumors which remain a challenge. In this book a review of the latest information on these topics along with a variety of new therapeutic treatment strategies with an emphasis on molecular targeted therapies is provided.

Brain Tumor Invasion Biological, Clinical, and Therapeutic Considerations Edited by Tom Mikkelsen Rolf Bjerkvig Ole Didrik Laerum Mark L. Rosenblum Recent advances in molecular biology have given us profound new insights into the behavior of primary brain tumors. Not only are such tumors more diffuse in their infiltration of brain tissue and therefore less amenable to surgery than brain tumors originating elsewhere in the body—it now appears that the central nervous system and the normal brain itself constitute a biological environment conducive to the uncontrolled spread of primary tumors. Brain Tumor Invasion is the first comprehensive reference devoted to the invasive behavior of primary brain tumors. It examines the biological mechanisms responsible for the increased ability of gliomas to metastasize in the central nervous system, and discusses the role of chemical carcinogens, growth factors, oncogenes, and tumor suppressors in the progression of such metastases. This book surveys the latest research in the field, reviews present and future prospects of anti-invasive brain tumor therapy, and even translates preclinical trials and other research results into potential new therapies. The material is divided into five main categories: Developmental biology and molecular neuro-oncology Pathological and clinical features of malignant brain tumors Models for the study of brain tumor invasion in vivo and in vitro Mechanisms of invasion New therapeutic strategies Brain Tumor Invasion offers dozens of maps and photographs that illustrate topics under discussion. This in-depth introduction to one of the most difficult problems in the management of brain tumors is indispensable to neuro-oncologists involved in brain tumor research and therapy. It is also useful to researchers in cancer biology, neuroscience, cell biology, and molecular genetics.

Childhood brain tumors are a diverse group of diseases characterized by the abnormal growth of tissue contained within the skull. Other than leukemia and lymphoma, brain tumors are the most common type of neoplasms that occur in children. The leading cause of death from childhood neoplasms among persons up to 19 years is brain tumors. As such, this book is a review of the most recent molecular biological research concerning brain tumors with references and comparisons to a variety of neoplastic disorders. The book then uses this information to foreshadow the direction that future anti-neoplastic therapies will take. Because of the wide spectrum of the objectives of the book, any individual involved in cancer research will greatly benefit from the work. Histopathologists, neuropathologists, clinical and research oncologists, and medical students will find this book to be an invaluable resource as a reference guide. Patients and their families will also find the book useful as it offers a comprehensive update on new, non-classical therapeutic modality options and contains a detailed description and analysis of brain tumors. Such an endeavor has yet to be undertaken by any other book and may prove to be the most comprehensive book on brain tumors thus far.

A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years. In particular, recent new avenues regarding the role of microRNAs along with further understanding of the importance of angiogenesis, immunotherapy and explanations for the resistance of the tumors to radiation therapy have been developed. A discussion of certain surgical management issues including improvements in imaging along with issues concerning tumor induced epilepsy is included. It is hopeful that this new information will lead to efficacious treatment strategies for these tumors which remain a challenge. In this book, a review of the latest information on these topics along with a variety of new therapeutic treatment strategies with an emphasis on molecular targeted therapies is provided.

Exciting new developments and discoveries of the last two decades are beginning to shed light on the complex biology of brain tumors and are advancing our understa- ing of the cellular and molecular processes involved in their initiation, progression, and clinical and biological behavior. The disease process in brain tumors is quite complex and the resulting tumors are characterized by a high degree of biological and clinical diversity. Thus, despite the advances of the last two decades, prognosis for patients with malignant brain tumors remains abysmal. Significant progress in the diagnosis, treatment and, ultimately, prevention of these tumors will require both the timely h- nessing of the advances in basic and clinical brain tumor research, and a continuing concerted effort at increasing our understanding of brain tumor biology, in particular, the molecular genetic changes and perturbations of cellular pathways involved in brain oncogenesis and which drive the biological and clinical behavior of the tumors. Brain tumor diagnosis and prognosis, which is still largely based on histopathology and other clinical criteria, will, in the future, acquire a significant molecular component, with the incorporation of knowledge of genes that are mutated, over-expressed, deleted, silenced, or functionally altered in the tumors. Treatment strategies for brain tumors, rather than being empirical, will be rationally developed based on an understanding of the cellular and molecular mechanisms and targets that have been activated, suppressed, or otherwise altered.

This volume mainly contains information on the diagnosis, therapy, and prognosis of brain tumors. Insights on the understanding of molecular pathways involved in tumor biology are explained, which should lead to the development of effective drugs. Information on pathways (e.g., hedgehog) facilitates targeted therapies in cancer. Tumor models are also presented, which utilize expression data, pathway sensitivity, and genetic abnormalities, representing targets in cancer. For example, rat model of malignant brain tumors using implantation of doxorubicin with drug eluting beads for delivery is explained. The future of pathway-driven therapies for tumors is summarized. The importance of personalizing cancer care is emphasized. The need for supportive measures for survivors of brain cancer is pointed out, so is the quality of life monitoring. The need of rehabilitation therapy for patients with primary and metastatic brain tumors is also emphasized. Role of MicroRNA in distinguishing primary tumors from metastatic primary tumors is discussed. Advantages and limitations of chemotherapy (e.g., temozolomide and doxorubicin) are discussed. The complexity of tumor to tumor transfer is explained; examples discussed are: brain metastases from breast cancer and brain metastases fro non-small cell lung carcinoma. Identification and characterization of biomarkers, including those for metastatic brain tumors, are presented. Genomic analysis for identifying clinically relevant subtypes of glioblastoma is included. A large number of imaging modalities are detailed to study progression and invasion of gliomas

A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years, and this has lead to the development of novel therapeutic strategies for these patients. In this book a review of the options available for the clinical management of patients with these tumors are outlined. In addition advances in radiology both for pre-operative diagnostic purposes along with surgical planning are described. Furthermore a review of newer developments in chemotherapy along with the evolving field of photodynamic therapy both for intra-operative management and subsequent therapy is provided. A discussion of certain surgical management issues along with tumor induced epilepsy is included. Finally a discussion of the management of certain unique problems including brain metastases, brainstem glioma, central nervous system lymphoma along with issues involving patients with a brain tumor and pregnancy is provided.

The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.