Abstract
Alterations of the epigenetic machinery are critically involved in cancer development and maintenance; therefore, the proteins in charge of the generation of epigenetic modifications are being actively studied as potential targets for anticancer therapies. A very important and widespread epigenetic mark is the dimethylation of Histone 3 in Lysine 36 (H3K36me2). Until recently, it was considered as merely an intermediate towards the generation of the trimethylated form, but recent data support a more specific role in many aspects of genome regulation. H3K36 dimethylation is mainly carried out by proteins of the Nuclear SET Domain (NSD) family, among which NSD2 is one of the most relevant members with a key role in normal hematopoietic development. Consequently, NSD2 is frequently altered in several types of tumors—especially in hematological malignancies. Herein, we discuss the role of NSD2 in these pathological processes, and we review the most recent findings in the development of new compounds aimed against the oncogenic forms of this novel anticancer candidate.
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