Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-10-25
pubmed:abstractText
Few chemotherapy agents have demonstrated activity in patients with myelodysplastic syndromes (MDS) and supportive management remains the standard of care. An increasing number of new drugs in development are being directed at specific molecular or biological targets of these diseases. Topotecan, a topoisomerase I inhibitor, has shown single-agent activity and is now being combined with other agents, including cytarabine. The aminothiol amifostine induces responses in about 30% of patients; however, its role is still being clarified. Agents that inhibit histone deacetylase and target DNA hypermethylation, thus permitting derepression of normal genes, include 5-azacytidine, decitabine, phenylbutyrate, and depsipeptide. Arsenic trioxide has demonstrated impressive activity in acute promyelocytic leukemia and preclinical data suggest the potential for activity in MDS. UCN-01 is a novel agent that inhibits protein kinase C and other protein kinases important for progression through the G1 and G2 phases of the cell cycle. Dolastatin-10 has extremely potent in vitro activity against a variety of tumor cell lines. Since its dose-limiting toxicities include myelosuppression, it is being studied in acute myelogenous leukemia (AML) and MDS. Ras may play a role in MDS, and activation of this gene and its signaling pathways may require farnesylation. Several farnesyl transferase inhibitors are now available for study in patients with MDS. An increasing body of data suggests a possible role for angiogenesis in MDS, and several antiangiogenesis agents are in clinical trials, including thalidomide, SU5416, and anti-vascular endothelial growth factor (VEGF) antibodies. Development of new drugs and regimens will be facilitated by recently developed standardized response criteria. Future clinical trials should focus on rational combinations of these agents and others with the goal of curing patients with MDS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0093-7754
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
560-77
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Novel therapeutic agents for the treatment of myelodysplastic syndromes.
pubmed:affiliation
Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Review