Epigenetic therapy for myelodysplastic syndromes has entered center stage

Abstract

These proceedings of the “Optimizing Epigenetic Therapies: Issues and Strategies” educational session held during the 10th International Symposium on Myelodysplastic Syndromes (Patras, Greece, May 6–9, 2009) have explored this very topical subject. In contrast to cytotoxic therapy, which attempts to directly destroy tumor cells, the goal of non-intensive epigenetic therapy is to modulate the behavior of abnormal cells by “re-programming” their gene expression profiles (e.g. by de-repression of tumor suppressor genes). Together with the Cancer and Leukemia Group B (CALGB), Dr Lewis Silverman (Mount Sinai School of Medicine, New York, NY, USA) has pioneered this approach in landmark phase II and III trials of the ribonucleoside azacitidine in patients with myelodysplastic syndromes (MDS) [1,2]. His groundbreaking work led to the phase III trial that compared low-dose azacitidine with conventional care regimens, such as sole best supportive care, low-dose cytarabine, or, in selected patients, conventional chemotherapy [3]. As outlined by Professor Pierre Fenaux (Hopital Avicenne, Assistance Publique–Hopitaux de Paris, Universite Paris XIII, Bobigny, France), this pivotal study first proved prolongation of overall survival with any MDS treatment. In a parallel development driven by both European and North American groups, decitabine, the sister compound of azacitidine, also demonstrated efficacy in older MDS patients with frequently adverse cytogenetics [4]. As described by Dr David Steensma (Dana Farber Cancer Institute, Boston, MA, USA), decitabine has shown efficacy in terms of both response rate and progression-free survival [5,6].