laromustine and tipifarnib

Preliminary therapeutic successes have prompted a new wave of clinical trials enrolling patients with myelodysplastic syndromes (MDS), using compounds with a broad range of potential mechanisms of action. This article discusses several of the agents currently in development for MDS, reviewing clinical trial data related to five classes of novel therapeutics: clofarabine, a halogenated purine nucleoside analog; ezatiostat (TLK199), a glutathione analog that indirectly activates c-Jun kinase; tipifarnib, a farnesyltransferase inhibitor; laromustine (cloretazine), an alkylating agent with a metabolite that inhibits one mechanism of DNA damage repair; and eight drugs that inhibit histone deacetylase. Although MDS are still difficult clinical problems, and most patients with MDS still succumb to disease-related complications within 3 to 5 years of diagnosis, ongoing development of novel agents promises that there will be new treatment options for patients within the next 5 to 10 years.

Topics: Adenine Nucleotides; Aged; Alkylating Agents; Antimetabolites; Arabinonucleosides; Clinical Trials as Topic; Clofarabine; DNA Repair; Drug Therapy, Combination; Drugs, Investigational; Enzyme Activation; Enzyme Inhibitors; Farnesyltranstransferase; Glutathione; Histone Deacetylase Inhibitors; Humans; Hydrazines; JNK Mitogen-Activated Protein Kinases; Myelodysplastic Syndromes; Quinolones; Sulfonamides; Therapies, Investigational

Topics: Adenine Nucleotides; Antineoplastic Agents; Arabinonucleosides; Azacitidine; Carbazoles; Clofarabine; Decitabine; Enzyme Inhibitors; Furans; Humans; Hydrazines; Immunotherapy; Lenalidomide; Leukemia, Myeloid, Acute; Quinolones; Staurosporine; Sulfonamides; Thalidomide