Research Article: Combined Bezafibrate and Medroxyprogesterone Acetate: Potential Novel Therapy for Acute Myeloid Leukaemia

Date Published: December 7, 2009

Publisher: Public Library of Science

Author(s): Farhat L. Khanim, Rachel E. Hayden, Jane Birtwistle, Alessia Lodi, Stefano Tiziani, Nicholas J. Davies, Jon P. Ride, Mark R. Viant, Ulrich L. Gunther, Joanne C. Mountford, Heinrich Schrewe, Richard M. Green, Jim A. Murray, Mark T. Drayson, Chris M. Bunce, Michael Goodyear.

Abstract: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis.

Partial Text: Acute myeloid leukaemia (AML) is a devastating cancer characterised by the uncontrolled proliferation, abnormal survival and arrested maturation of leukaemic cells within the bone marrow. The rapid expansion of the leukaemic clone reduces haemopoiesis with loss of normal functioning neutrophils, platelets, and erythrocytes. If untreated, most patients die from infection, bleeding and/or anaemia within weeks of diagnosis.

Drug redeployment has already demonstrated great promise in haemato-lymphoid malignancies including, thalidomide in myeloma [59] and valproic acid and arsenic trioxide in AML [60], [61]. However, few studies have sought to redeploy combinations of old drugs that deliver greater potency than either drug alone. We demonstrate here that exploiting some understanding of the mechanisms of drug actions against cancer cells allows the rational testing of such potentially beneficial combinations.



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