title: Molecular pathways: targeting RAC-p21-activated serine-threonine kinase signaling in RAS-driven cancers.
abstract: Cancers driven by oncogenic Ras proteins encompass some of the most deadly human cancer types, and there is a pressing need to develop therapies for these diseases. Although recent studies suggest that mutant Ras proteins may yet be druggable, the most promising and advanced efforts involve inhibitors of Ras effector signaling. Most efforts to target Ras signaling have been aimed at the ERK mitogen-activated protein kinase and the phosphoinositide 3-kinase signaling networks. However, to date, no inhibitors of these Ras effector pathways have been effective against RAS-mutant cancers. This ineffectiveness is due, in part, to the involvement of additional effectors in Ras-dependent cancer growth, such as the Rac small GTPase and the p21-activated serine-threonine kinases (PAK). PAK proteins are involved in many survival, cell motility, and proliferative pathways in the cell and may present a viable new target in Ras-driven cancers. In this review, we address the role and therapeutic potential of Rac and group I PAK proteins in driving mutant Ras cancers.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Baker
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Hoi
authors.initials: H
authors.lastname: Yee Chow
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. cjder@med.unc.edu.
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases