Translational regulation as a novel mechanism for the development of cellular drug resistance.
Cellular drug resistance is one of the principal obstacles to the clinical efficacy of cancer chemotherapy. In this review, we describe the potential role for translational regulation as a novel mechanism for modulating chemosensitivity. The evidence for the translational control of thymidylate synthase, dihydrofolate reductase, and p53 will be presented, as will experimental data showing how disruptions in this important regulatory process can lead to the rapid emergence of cellular drug resistance.
Schmitz
J C
JC
Department of Medicine and Pharmacology, Yale Cancer Center, Yale University School of Medicine and VA CT Cancer Center, VA CT Healthcare System, New Haven 06516, USA.
Liu
J
J
Lin
X
X
Chen
T M
TM
Yan
W
W
Tai
N
N
Gollerkeri
A
A
Chu
E
E
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D014176:Protein Biosynthesis; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase