New nucleoside analogs in the treatment of hematological disorders.
Cytotoxic nucleoside analogs have a broad clinical use. They were among the first chemotherapeutic agents used in the treatment of malignant diseases. The anticancer nucleosides include analogs of physiologic pyrimidine and purine nucleosides. They are used in oncology in the treatment of both, solid tumors and hematological malignancies. These agents have many intracellular targets, e.g. they act as antimetabolites, competing with natural nucleosides during DNA or RNA synthesis and as inhibitors of key cell enzymes. Understanding of the mechanisms of action of these compounds and synthesis of new analogs provides the possibility to further expand the spectrum of their clinical use and enhance their antitumor activity. In this paper we describe mechanisms of action and possible clinical use in the treatment of hematological malignancies of these nucleoside analogs, which are now in different stages of clinical trials, namely tezacitabine, troxacitabine, clofarabine, nelarabine, decitabine, CNDAC and ECyD.
Szafraniec
Sylwia I
SI
Flow Cytometry Laboratory, National Institute of Public Health, 30/34 Chelmska Str, 00-725 Warsaw, Poland.
Stachnik
Krzysztof J
KJ
Skierski
Janusz S
JS
D000227:Adenine Nucleotides; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077866:Clofarabine; D003561:Cytarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004148:Dioxolanes / Q000009:adverse effects / Q000627:therapeutic use; D006207:Half-Life; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D011684:Purine Nucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D011741:Pyrimidine Nucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D013237:Stereoisomerism
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D004148:Dioxolanes; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D003561:Cytarabine; D003841:Deoxycytidine; C070279:2'-cyano-2'-deoxyarabinofuranosylcytosine; C104457:nelarabine; C074908:troxacitabine; D000077866:Clofarabine; D003596:Cytosine; C086432:tezacitabine