title: Unlocking the potential of retinoic acid in anticancer therapy.
abstract: All-trans-retinoic acid (ATRA) is a physiologically active metabolite of vitamin A. Its antitumour activities have been extensively studied in a variety of model systems and clinical trials; however, to date the only malignancy responsive to ATRA treatment is acute promyelocytic leukaemia (APL) where it induces complete remission in the majority of cases when administered in combination with light chemotherapy and/or arsenic trioxide. After decades of studies, the efficacy of ATRA to treat other acute myeloid leukaemia (AML) subtypes and solid tumours remains poor. Recent studies directed to improve ATRA responsiveness in non-APL AML seem to indicate that the lack of effective ATRA response in these tumours may be primarily due to aberrant epigenetics, which negatively affect ATRA-regulated gene expression and its antileukaemic activity. Epigenetic reprogramming could potentially restore therapeutic effects of ATRA in all AML subtypes. This review discusses the current progresses in the understanding how ATRA can be utilised in the therapy of non-APL AML and other cancers.
authors.affiliation: Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, 123 Old Brompton Road, SW7 3RP London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Schenk
authors.affiliation: Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, 123 Old Brompton Road, SW7 3RP London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Stengel
authors.affiliation: Division of Hemato-Oncology, Department of Medicine, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1550 NW 10th Avenue, Miami, FL 33136, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zelent
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D018168:Receptors, Retinoic Acid / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D014212:Tretinoin