title: Dragging ras back in the ring.
abstract: Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras oncoproteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers.
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Stephen
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Esposito
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Bagni
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA; UCSF Helen Diller Family Comprehensive Cancer Center, Room 371, 1450 3(rd) Street, P.O. Box 589001, San Francisco, CA 94158-9001, USA. Electronic address: mccormic@cc.ucsf.edu.
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
mesh_terms: D000818:Animals; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D012192:Retroviridae Infections / Q000188:drug therapy; D015398:Signal Transduction; D014412:Tumor Virus Infections / Q000188:drug therapy
chemical_list: D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D015689:Oncogene Protein p21(ras); D016283:Proto-Oncogene Proteins p21(ras)