Introduction of arsenic trioxide（ATO, As_2O_3） to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent＇s fur...Introduction of arsenic trioxide（ATO, As_2O_3） to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent＇s further functions has rapidly advanced so that it has entered common use in hematology and oncology. In addition, As_2O_3 reportedly induces DNA and chromosomal damage, inhibits DNA repair, and alters DNA methylation in mammalian cells. The compound is becoming increasingly reasonable as a treatment modality to rectify genetic blood disorders and other cancer types. Nevertheless, limitations of As_2O_3 typically emerged from drug resistance, adverse effects and secondary tumors, which may result in a myriad of outcomes. Though prolonged exposure to As_2O_3 ensues poisons and genome alternations that do not permanently change the DNA sequence, other synergistic alterations should be considered as replacement. In this review, we recollect the discovery and clinical implementation of As_2O_3, describe its advantages and shortcomings for leukemia and solid cancer treatment, and consider future prospects for engendering useful impacts.展开更多
基金National Natural Science Foundation(81430088)Grants from Special Fund for Doctor Stations,Ministry of Education,China(20122307130003)
文摘Introduction of arsenic trioxide（ATO, As_2O_3） to the treatment of acute promyelocytic leukemia in the 1970s enlightened an effective treatment approach for the disease. Decades later, knowledge on this agent＇s further functions has rapidly advanced so that it has entered common use in hematology and oncology. In addition, As_2O_3 reportedly induces DNA and chromosomal damage, inhibits DNA repair, and alters DNA methylation in mammalian cells. The compound is becoming increasingly reasonable as a treatment modality to rectify genetic blood disorders and other cancer types. Nevertheless, limitations of As_2O_3 typically emerged from drug resistance, adverse effects and secondary tumors, which may result in a myriad of outcomes. Though prolonged exposure to As_2O_3 ensues poisons and genome alternations that do not permanently change the DNA sequence, other synergistic alterations should be considered as replacement. In this review, we recollect the discovery and clinical implementation of As_2O_3, describe its advantages and shortcomings for leukemia and solid cancer treatment, and consider future prospects for engendering useful impacts.
