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Despite considerable advances in our understanding of the molecular and epigenetic underpinnings of the myelodysplastic syndromes (MDS), this diverse group of myeloid neoplasms remains a significant clinical challenge. Considerable barriers to timely development of effective therapy include the diverse molecular landscape encountered in MDS patients, the difficulty in translating specific molecular aberration into a clinically meaningful animal model, as well as challenges in patient recruitment into clinical trials. These speak to the need to discover efficacious novel therapeutic targets which would in turn translate into improved patient outcomes in terms of both survival and quality of life. In this review, we outline recently published data pertaining to therapeutic advances in TGF-β pathway inhibition, STAT3, Hedgehog signaling, and additional therapeutic venues being actively explored in MDS.

The therapeutic paradigm for treatment of acute myeloid leukemia (AML) is rapidly changing with the advent of a new generation of drugs targeting diverse aspects of leukemogenesis. Whereas standard treatment for AML until recently consisted of a classic chemotherapy backbone, the incorporation of novel agents targeting pathogenic mutations, myeloid surface markers, and apoptosis-related proteins may become a reality in the next few years. In this review, we outline the therapeutic landscape of recently approved novel agents for AML, including FLT3 inhibitors, isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors, Bcl-2 antagonists, hedgehog signaling inhibitors, and immunotherapy-based approaches. Some of the future challenges in the field would be to delineate which specific patient subsets derive the most clinical benefit from a given novel agent and, furthermore, which drug combinations will yield the maximal antileukemia effect without increased toxicity. To this end, it is expected that advances in genomic and epigenomic classification of AML will facilitate a rational and optimal choice of these novel agents for AML patients.