Open AccessCombination therapies improve the anticancer activities of retinoids in neuroblastoma
Author(s) -
Belamy B. Cheung
Publication year - 2015
Publication title -
world journal of clinical oncology
Language(s) - English
Resource type - Journals
ISSN - 2218-4333
DOI - 10.5306/wjco.v6.i6.212
Subject(s) - medicine , retinoid , neuroblastoma , histone deacetylase , histone deacetylase inhibitor , cancer research , vorinostat , chemotherapy , retinoic acid , combination therapy , fenretinide , cancer , oncology , pharmacology , tretinoin , minimal residual disease , histone , leukemia , biology , cell culture , biochemistry , gene , genetics
Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index, and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy, death still occurs due to relapse of persistent minimal residual disease (MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma (NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD, yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies, with a lower side-effect profile, are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and -independent signalling mechanisms. Moreover, several histone deacetylase inhibitors have entered early phase trials, and, suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies.