Future Of Experimental Therapy In

A number of single agents belonging to different classes of drugs have now been found to be of benefit for subsets of MDS patients. Targeted therapies, such as ima-tinib for patients with fusion proteins resulting from abnormalities of 4(q12) or t(5;12), and lenalidomide in patients with 5q-, are likely to remain restricted to small subsets of MDS patients. For the vast majority of both low- and high-risk patients, the challenge is to match the right drug with the individual needs of the patient. While ever-evolving biologic insights are providing a better and more healthy rationale for specific therapies, the ability to administer a single drug as a result of such insights is still a faraway dream. In AML, both ara-C and anthracyclines as single agents produced complete responses in approximately 30% of patients. It was only when the two drugs were combined in the so-called 7 + 3 regimen that we began to see the synergy and additive effects, with remission rates in the 60-70% range. Applying the same lessons to MDS, it is clear that while we are finally starting to witness responses to singleagent therapy in subsets of patients, the future lies in developing combination trials. As a general rule, it would be worthwhile to consider combining agents that target the clone of MDS cells with those that target the bone marrow microenvironment, so that both the seed and the soil are simultaneously affected. Examples of future combination trials would be the use of agents like DNA methyltransferase inhibitors, FTIs, TKIs, and arsenic with antiangiogenic, anti-TNF, and immune-modulatory drugs. In the final analysis, it is an exciting time to be involved in translational research in MDS as the last two decades have taken us from having nothing to offer our patients save supportive care, to having almost an embarrassment of riches. One drug has already been approved for use in this disease, and several others are approaching approval.

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