A new paradigm has emerged showing that the immune system can influence cancer cell epigenetics through NF-κB–mediated regulation of TET1.

rowing evidence suggests that chemical modifications on RNA, similar to those on DNA or histones, control gene expression 1 . More than 100 types of RNA modifications have been reported 2 , among which m 6 A is the most abundant internal modification 3 . Transcriptome-wide mappings of m 6 A identified methylated sites in more than 7,000 mRNA transcripts, many conserved between humans and mice 3,4 . Marking with m 6 A occurs on adenosines embedded in the consensus sequence G(G > A) m 6 ACU, especially in 3′-untranslated regions (UTRs) near stop codons of transcripts 5 . Installed by the METTL3/METTL14/WTAP methyltransferase complex and erased by the demethylases FTO and ALKBH5 (refs. 6,7 ), m 6 A influences fundamental aspects of mRNA metabolism, such as mRNA stability, splicing, transport and translation, thereby impacting gene expression [3][4][5][8][9][10][11][12] .FTO was found to catalyze m 6 A demethylation in an Fe(II)-and α-ketoglutarate-dependent enzymatic reaction 6,13,14 . In addition to an involvement in essential biological processes 5,8 , FTO has been linked to cancer, acting as an oncoprotein in leukemia 15,16 . Despite conflicting results by Vu et al., who observed no substantial effect of FTO depletion on acute myeloid leukemia (AML) cell viability 17 , the development of FTO inhibitors has since shown encouraging results in preclinical settings 16,18,19 . Similar oncogene functions were

Background Percutaneous endoscopic gastrostomy (PEG) is often used to provide nutritional support in locally advanced head and neck cancer patients undergoing multimodality treatment. However, there is little published data on the impact of prophylactic versus reactive PEG. PEG placement may affect swallowing-related physiology, function, and quality of life. The Swall PEG study is a randomized controlled phase III trial testing the impact of prophylactic versus reactive PEG on patient-reported outcomes in terms of swallowing and quality of life in oropharyngeal cancer patients. Methods Patients with locally advanced oropharyngeal cancer receiving chemo-radiotherapy will be randomized to either the prophylactic or reactive PEG tube group. Randomization will be stratified by human papillomavirus (HPV) status and unilateral versus bilateral positive neck lymph nodes. The primary objective of the study is the patient’s reported outcome in terms of swallowing (MD Anderson Dysphagia Inventory (MDADI)) at 6 months. Secondary objectives include health-related quality of life, dosimetric parameters associated with patient-reported outcomes, chemo-radiation toxicities, PEG tube placement complications, the impact of nutritional status on survival and toxicity outcomes, loco-regional control, overall survival, the impact of HPV and tobacco smoking on survival outcomes and toxicities, and the cost-effectiveness of each treatment strategy. Discussion Findings from this study will enhance clinical evidence regarding nutritional management in oropharyngeal cancer patients treated by concurrent chemo-radiation. Trial registration ClinicalTrials.gov NCT04019548, study protocol version 2.0_08/08/2019. Registered on 15 July 2019