TY - JOUR
T1 - Emerging treatments for myelodysplastic syndromes
T2 - Biological rationales and clinical translation
AU - Rodriguez-Sevilla, Juan Jose
AU - Adema, Vera
AU - Garcia-Manero, Guillermo
AU - Colla, Simona
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/2/21
Y1 - 2023/2/21
N2 - Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, nearly 50% of patients have no response to the treatment. Patients with MDS in whom HMA therapy has failed have a dismal prognosis and no approved second-line therapy options, so enrollment in clinical trials of experimental agents represents these patients’ only chance for improved outcomes. A better understanding of the molecular and biological mechanisms underpinning MDS pathogenesis has enabled the development of new agents that target molecular alterations, cell death regulators, signaling pathways, and immune regulatory proteins in MDS. Here, we review novel therapies for patients with MDS in whom HMA therapy has failed, with an emphasis on the biological rationale for these therapies’ development.
AB - Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, nearly 50% of patients have no response to the treatment. Patients with MDS in whom HMA therapy has failed have a dismal prognosis and no approved second-line therapy options, so enrollment in clinical trials of experimental agents represents these patients’ only chance for improved outcomes. A better understanding of the molecular and biological mechanisms underpinning MDS pathogenesis has enabled the development of new agents that target molecular alterations, cell death regulators, signaling pathways, and immune regulatory proteins in MDS. Here, we review novel therapies for patients with MDS in whom HMA therapy has failed, with an emphasis on the biological rationale for these therapies’ development.
KW - hypomethylating agents
KW - myelodysplastic syndromes
KW - novel therapeutic agents
KW - secondary acute myeloid leukemia
UR - http://www.scopus.com/inward/record.url?scp=85148678482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148678482&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.100940
DO - 10.1016/j.xcrm.2023.100940
M3 - Review article
C2 - 36787738
AN - SCOPUS:85148678482
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 2
M1 - 100940
ER -