Advances in targeting RNA modifications for anticancer therapy

Abstract

Numerous strategies are employed by cancer cells to control gene expression and facilitate tumorigenesis. In the study of epitranscriptomics, a diverse set of modifications to RNA represent a new player of gene regulation in disease and in development. N⁶-methyladenosine (m⁶A) is the most common modification on mammalian messenger RNA and tends to be aberrantly placed in cancer. Recognized by a series of reader proteins that dictate the fate of the RNA, m⁶A-modified RNA could promote tumorigenesis by driving protumor gene expression signatures and altering the immunologic response to tumors. Preclinical evidence suggests m⁶A writer, reader, and eraser proteins are attractive therapeutic targets. First-in-human studies are currently testing small molecule inhibition against the methyltransferase-like 3 (METTL3)/methyltransferase-like 14 (METTL14) methyltransferase complex. Additional modifications to RNA are adopted by cancers to drive tumor development and are under investigation.

Keywords: METTL3; N(6)-methyladenosine; RNA modifications; cancer; epitranscriptomics.