title: Emerging biological therapies for the treatment of myelodysplastic syndromes.
abstract: BACKGROUND
  No drug has resulted in a survival advantage in patients with lower-risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have revolutionized treatment options for patients with higher-risk MDS, the prognosis remains dismal after HMA treatment failure. Novel effective therapies are urgently needed especially after HMA failure.
  
  
  METHODS
  This review covers the current approach to disease prognostication and risk-adaptive therapy, as well as novel therapeutic approaches. We discuss the recent advancements in the understanding of MDS disease biology as a basis of targeted drug development. Several classes of novel agents are reviewed including drugs targeting dysregulated epigenetic control mechanisms, signaling pathways, abnormal splicing, as well as agents that target the immune system and the MDS bone marrow niche.
  
  
  CONCLUSIONS
  Significant advancements in the understanding of the underlying biology of MDS are only starting to be translated into novel treatment options for MDS. Epigenetic therapy has shown significant clinical activity with HMA but the results of clinical trials combining HMAs with histone deacetylase inhibitors (HDACi) have been disappointing to date. Similarly, targeting several aberrant pathways in MDS has not resulted in significant improvements in therapy. Future therapies will focus both on synergic combination of existing drugs as well as novel agents targeting dysregulated immune responses and abnormal RNA splicing in MDS.
authors.affiliation: a Department of Internal Medicine, Section of Hematology , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Amer M
authors.initials: AM
authors.lastname: Zeidan
authors.affiliation: b Department of Internal Medicine , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stahl
authors.affiliation: c Oncologic Sciences , University of South Florida College of Medicine , Tampa , Florida.|d Department of Malignant Hematology , Moffitt Cancer Center , Tampa , Florida.
authors.forename: Rami
authors.initials: R
authors.lastname: Komrokji
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods; D015195:Drug Design; D044127:Epigenesis, Genetic; D006801:Humans; D058990:Molecular Targeted Therapy; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D012326:RNA Splicing
keywords: MDS; epigenetics; hypomethylating agents; splicing; therapeutics