RNA modification enzyme FTO shows therapeutic promise in gastrointestinal cancers

A new review in Genes & Diseases highlights FTO, an enzyme involved in RNA modification, as a potentially important biomarker and therapeutic target across gastrointestinal cancers. The article brings together current understanding of FTO in gastric, liver, colorectal and pancreatic cancers, revealing a complex role in which the enzyme can both promote and suppress cancer progression depending on biological context.

FTO is an RNA demethylase capable of removing chemical modifications including N6-methyladenosine (m6A). Through this activity, FTO can influence RNA stability, translation, degradation and movement within cells. These processes can ultimately affect how cancer cells grow, spread, respond to their environment and withstand treatment.

Across gastrointestinal cancers, FTO is associated with pathways controlling tumour growth, metastasis, metabolic reprogramming, immune escape, ferroptosis and treatment resistance. Importantly, its effects are not uniform. FTO can function as an oncogenic factor in some circumstances while suppressing tumour progression in others. This dual role indicates that targeting FTO will require careful consideration of the molecular and cancer-specific context.

The review also highlights the extensive mechanisms that regulate FTO. Transcription factors, RNA-related regulators and epigenetic mechanisms can influence FTO expression, while post-translational modifications including acetylation, ubiquitination, SUMOylation and phosphorylation can affect its stability, cellular location, degradation and activity. Understanding these regulatory networks may reveal additional ways to control FTO more precisely.

A growing range of small-molecule FTO inhibitors further supports interest in the enzyme as a potential drug target. Compounds including Rhein, FB23-2, CS1/CS2, Dac51 and 18097 have demonstrated anticancer potential in experimental settings. Some FTO-targeting approaches may also complement immunotherapy, raising the possibility of future combination treatment strategies. However, clinical validation is still required, particularly for gastrointestinal cancers.