Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer.
Hongmiao WangHuixun JiaYang GaoHaosong ZhangJin FanLijie ZhangFandong RenYandong YinYuping CaiZeng-Fu ShangZheng-Jiang ZhuPublished in: Nature communications (2022)
Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). Therapeutic efficacy of nCRT is significantly affected by treatment-induced diarrhea and hematologic toxicities. Metabolic alternations in cancer therapy are key determinants to therapeutic toxicities and responses, but exploration in large-scale clinical studies remains limited. Here, we analyze 743 serum samples from 165 LARC patients recruited in a phase III clinical study using untargeted metabolomics and identify responsive metabolic traits over the course of nCRT. Pre-therapeutic serum metabolites successfully predict the chances of diarrhea and hematologic toxicities during nCRT. Particularly, levels of acyl carnitines are linked to sex disparity in nCRT-induced diarrhea. Finally, we show that differences in phenylalanine metabolism and essential amino acid metabolism may underlie distinct therapeutic responses of nCRT. This study illustrates the metabolic dynamics over the course of nCRT and provides potential to guide personalized nCRT treatment using responsive metabolic traits.
Keyphrases
- rectal cancer
- locally advanced
- neoadjuvant chemotherapy
- cancer therapy
- squamous cell carcinoma
- phase ii study
- genome wide
- radiation therapy
- end stage renal disease
- mass spectrometry
- amino acid
- newly diagnosed
- irritable bowel syndrome
- phase iii
- randomized controlled trial
- drug delivery
- high glucose
- clostridium difficile
- chronic kidney disease
- open label
- ms ms
- combination therapy
- dna methylation
- diabetic rats
- peritoneal dialysis
- patient reported outcomes
- drug induced
- study protocol
- fatty acid
- smoking cessation