Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients.

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S.

Identification of non-coding silencer elements and their regulation of gene expression.

Cell type- and differentiation-specific gene expression is precisely controlled by genomic non-coding regulatory elements (NCREs), which include promoters, enhancers, silencers and insulators. It is estimated that more than 90% of disease-associated sequence variants lie within the non-coding part of the genome, potentially affecting the activity of NCREs. Consequently, the functional annotation of NCREs is a major driver of genome research.