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Ras and Cancer in the 21st Century


Book Series:  A Cold Spring Harbor Perspectives in Medicine Collection
Subject Area(s):  Cell Biology

Edited by Linda Van Aelst, Cold Spring Harbor Laboratory; Julian Downward, The Francis Crick Institute; Frank McCormick, University of California, San Francisco

Download a Free Excerpt from Ras and Cancer in the 21st Century:

Preface
KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Index

© 2018 • 285 pages, illustrated (48 color and 9 B&W), index
Hardcover • $135 94.50
ISBN  978-1-621822-21-9
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  •     Description    
  •     Contents    

Description

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 biochemical characteristics of the different Ras isoforms (HRAS, KRAS, and NRAS), their main effectors and signaling pathways, and the mutations that lead to their constitutive activation. Recent work showing that some Ras oncoproteins may be effectively inhibited by small molecules is covered, as is work on alternative targets (e.g., enzymes that catalyze posttranslational modifications of Ras) and inhibitors (e.g., nucleic acids).

The authors also discuss how organoids and mouse models are being used to study tumor progression and therapeutic efficacy. This volume is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with understanding and treating Ras-driven cancers.

Contents

Preface
From Ras to Rap and Back, a Journey of 35 Years
Johannes L. Bos
Ras-Mediated Activation of the Raf Family Kinases
Elizabeth M. Terrell and Deborah K. Morrison
PI3K: A Crucial Piece in the RAS Signaling Puzzle
Agata Adelajda Krygowska and Esther Castellano
The Interdependent Activation of Son-of-Sevenless and Ras
Pradeep Bandaru, Yasushi Kondo, and John Kuriyan
Posttranslational Modifications of RAS Proteins
Ian Ahearn, Mo Zhou, and Mark R. Philips
Ras and the Plasma Membrane: A Complicated Relationship
Yong Zhou, Priyanka Prakash, Alemayehu A. Gorfe, and John F. Hancock
MRAS: A Close but Understudied Member of the RAS Family
Lucy C. Young and Pablo Rodriguez-Viciana
The K-Ras, N-Ras, and H-Ras Isoforms: Unique Conformational Preferences and Implications for Targeting Oncogenic Mutants
Jillian A. Parker and Carla Mattos
KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Andrew M. Waters and Channing J. Der
Mechanistic and Preclinical Insights from Mouse Models of Hematologic Cancer Characterized by Hyperactive Ras
Anica Wandler and Kevin Shannon
Genetically Engineered Mouse Models of K-Ras-Driven Lung and Pancreatic Tumors: Validation of Therapeutic Targets
Matthias Drosten, Carmen Guerra, and Mariano Barbacid
Kras in Organoids
Derek Cheng and David Tuveson
Kras and Tumor Immunity: Friend or Foe?
Jane Cullis, Shipra Das, and Dafna Bar-Sagi
Synthetic Lethal Vulnerabilities in KRAS-Mutant Cancers
Andrew J. Aguirre and William C. Hahn
Efforts to Develop KRAS Inhibitors
Matthew Holderfield
Targeting Ras with Macromolecules
Dehua Pei, Kuangyu Chen, and Hui Liao
Targeting the MAPK Pathway in RAS Mutant Cancers
Sarah G. Hymowitz and Shiva Malek
Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions
Klaus Scheffzek and Giridhar Shivalingaiah
Index