Targeting the K-Ras/PDEδ protein-protein interaction: the solution for Ras-driven cancers or just another therapeutic mirage?
The holy grail, finally? After years of unsuccessful attempts at drugging the Ras oncogene, a recent paper by Zimmerman et al. has revealed the possibility of inhibiting Ras signaling on a clinically relevant level by blocking the K-Ras/PDEδ protein-protein interaction. The results, reported in Nature, are highlighted herein with future implications and directions to evaluate the full clinical potential of this research.
Department of Pharmacology & Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721 (USA); BIO5 Oro Valley (BIO5OV), University of Arizona, 1580 E. Hanley Blvd, Oro Valley, AZ 85737 (USA).
Brendan
B
Frett
Yuanxiang
Y
Wang
Hong-Yu
HY
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C517432:PDE6D protein, human; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Ras; anticancer agents; drug resistance; protein–protein interactions; targeted therapeutics