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Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. Mutations that produce abnormally active Ras proteins are common in human cancers, particularly those of the pancreas, lung, and colon. These cancers can be difficult to treat because Ras oncoproteins have long been considered 'undruggable.' Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the recent progress that has been made in understanding Ras biology, how Ras activation leads to tumorigenesis, and ways in which oncogenic Ras signaling may be targeted therapeutically. The contributors review the bioc...
The Ras superfamily (>150 human members) encompasses Ras GTPases involved in cell proliferation, Rho GTPases involved in regulating the cytoskeleton, Rab GTPases involved in membrane targeting/fusion and a group of GTPases including Sar1, Arf, Arl and dynamin involved in vesicle budding/fission. These GTPases act as molecular switches and their activities are controlled by a large number of regulatory molecules that affect either GTP loading (guanine nucleotide exchange factors or GEFs) or GTP hydrolysis (GTPase activating proteins or GAPs). In their active state, they interact with a continually increasing, functionally complex array of downstream effectors. Since the last Methods in Enzymo...
The critically acclaimed laboratory standard for more than 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today-truly an essential publication for researchers in all fields of life sciences.This volume and its companions (Volumes 255, 256, 257, and the forthcoming 325, 329, and 332) cover all biochemical and biological assays currently in use for analyzing the role of small GTPases in the above-mentioned aspects of cell biology at the molecular level.
Since 1982, Ras proteins have been the subject of intense research investigation by the biomedical research community. The wide interest in Ras has been stimulated for three key reasons. This book features chapters contributed by leading investigators in the field that highlight the current state-of-the art in Ras biochemistry, structure and biology. This book is an excellent reference for students in the biomedical sciences and for investigators in the field.
Proceedings of the workshop held Nov. 1988. Ras genes constitute an important family among the fifty oncogenes which have been discovered so far, and they contribute significantly to the human tumor burden since around 70% of human tumors have an increased level of ras gene product and 40% carry a m
This book, which was written by the current leaders in the field of Ras research, provides the readers with the most comprehensive and up-to-date view of the major oncogene Ras. This volume is valuable not only for university students in molecular biology, biochemistry or medicine, but also for senior scientists currently conducting cancer research.
since the earliest results on the linkage between ras activation and cell transformation appeared a vast amount of additional information has been generated which emphasizes the importance of ras-related genes in membrane trafficking, cell proliferation, differentiation and cancer. These advances led to the development of new strategies for the diagnosis, prognosis and prevention of cancer. Ras-related genes appear to be central to the mechanism of transformation by other oncogenes and therefore constitute a focal point upon which attempts to intervene in the process of carcinogenesis will be concentrated. The present volume contains the contributions to the NATO Advanced Research Workshop o...
KRAS Drug Discovery: Past, Present and Future is a comprehensive overview of the state-of-the-art medicinal chemistry approaches towards targeting the formerly undruggable oncogene, KRAS. It includes Seminal medicinal chemistry case histories of KRASG12C inhibitors such as Sotorosib, the first approved KRASG12C inhibitor for NSCLC, alongside the latest advances towards identification of in vivo tools and development candidates targeting KRAS G12D, KRAS G13C and other mutations. The book also provides the reader with a comprehensive overview of the in vitro assay systems, in vivo pharmacology xenograft models and chemical biology tools available to characterize small molecule inhibitors of KRAS. - Highlights key structure-based drug design (SBDD) innovations to generate potency and selectivity vs. KRAS - Analyzes medicinal chemistry case histories for seminal contributions to the KRAS field - Provides an overview of in vitro and in vivo methods for drugging KRAS
However, by that time the site had already seen more than 6,000 years of occupation, and the data from Ras Shamra - Ugarit thus have become important as a reference point for the early history of the Near East along the Levantine coast and the eastern Mediterranean."