ter-199 and Bone-Marrow-Diseases

As opposed to the treatment landscape for myelodysplastic syndromes (MDS) two decades ago, potential therapies now abound for the treatment of lower-risk and higher-risk populations. In lower-risk patients, decision tools can be used to determine the likelihood of response to erythropoiesis stimulating agents (ESAs), which have demonstrated survival advantages in retrospective studies in patients with MDS, and whether these patients should be treated initially with ESAs or non-growth factor ("active") therapies. Lenalidomide has shown good activity in transfusion-dependent patients with the del(5q) cytogenetic abnormality and modest activity in other lower-risk patients. In higher-risk patients, the DNA methyltransferase inhibitors produce complete and partial responses in 20% to 30% of patients, and for the first time, the MDS drug azacitidine has demonstrated a survival advantage when compared with conventional therapies. Newer therapies stimulate platelet production and target novel pathways, while a panoply of combination studies are underway or recently completed and that likely represent the next frontier in MDS therapy.

Topics: Azacitidine; Benzoates; Blood Transfusion; Bone Marrow Diseases; Chromosome Deletion; Chromosomes, Human, Pair 5; Clinical Trials as Topic; Combined Modality Therapy; Decitabine; DNA-Cytosine Methylases; Glutathione; Hematinics; Humans; Hydrazines; Immunologic Factors; Lenalidomide; Myelodysplastic Syndromes; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Risk; Thalidomide; Thrombopoietin

Telik Inc is developing TLK-199, an intravenous inhibitor of glutathione S-transferase P1-1, for the potential prevention of myelosuppression in blood diseases, namely myelodysplastic syndrome.

Topics: Animals; Bone Marrow Diseases; Enzyme Inhibitors; Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes