title: Omacetaxine as an anticancer therapeutic: what is old is new again.
abstract: Omacetaxine mepesuccinate was originally identified more than 35 years ago and initial studies in chronic myeloid leukemia (CML) showed promising activity. It has also been studied in other hematologic and solid tumors as both a single agent and in combination with other treatments. However, the introduction of imatinib and related tyrosine kinase inhibitors (TKIs) abated the clinical development of omacetaxine as a treatment for CML. The advent of resistance to imatinib and other TKIs in CML patients (often due to the presence of an ABL mutation at position 315) has led to a revived clinical interest in omacetaxine in CML patients who failed TKIs. Here we review omacetaxine's mechanism of action (MOA) as a protein translation inhibitor, how its MOA may translate into activity in treatment of cancers, its potential to eradicate leukemia initiating cells and other cancer stem cells and the potential significance of this activity in clinical practice.
authors.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo NY 14263, USA. meir.wetzler@roswellpark.org
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: David
authors.initials: D
authors.lastname: Segal
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006248:Harringtonines / Q000494:pharmacology / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008957:Models, Genetic; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D011500:Protein Synthesis Inhibitors; D000077863:Homoharringtonine