Retinoids--"differentiation agents" for cancer treatment and prevention.
The ability of vitamin A and its derivatives to induce differentiation in certain target tissues has been appreciated for nearly a century. Recently, oral all-trans retinoic acid (ATRA), a vitamin A metabolite, has been shown to induce terminal differentiation of leukemic cells in patients with acute promyelocytic leukemia (APL). Complete remissions are obtained and normal hematopoiesis is established in an outpatient setting with minimal side effects in the majority of cases. Although remissions are not durable, disseminated intravascular coagulation, a frequent complication of remission induction in APL, is avoided by oral ATRA prior to definitive chemotherapy. The molecular basis for the efficacy of ATRA in APL appears to be the involvement of the retinoic acid receptor alpha locus in the t(15;17) translocation breakpoint characteristic of APL.
Hofmann
S L
SL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8593.
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids / Q000627:therapeutic use*; D014157:Transcription Factors; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014212:Tretinoin; D004247:DNA