Abu‐Fares, Hala

Early-onset colorectal cancer (eoCRC) is increasing globally, raising interest in modifiable dietary exposures that may contribute to its development. High fructose intake, particularly from sugar-sweetened beverages and high-fructose corn syrup, has been associated with colorectal neoplasia and eoCRC in epidemiologic studies. Experimental evidence suggests that fructose may promote colorectal tumorigenesis through enhanced uptake and metabolism, polyol pathway activation, glycolytic and lipogenic reprogramming, hypoxic adaptation, and interactions with the tumor microenvironment. Excess fructose reaching the colon may also impair intestinal barrier integrity and alter gut microbial composition and metabolite production. Preclinical models support a direct tumor-promoting effect of fructose independent of obesity, whereas human mechanistic and microbiome data remain limited. This review summarizes current evidence linking fructose exposure with eoCRC and discusses emerging metabolic, microbial, and translational implications, while highlighting key gaps that must be addressed to establish causality and clinical relevance.

Abstract Purpose: CD4 T-cell immunity is associated with improved survival in patients with breast cancer. We previously reported a phase I trial evaluating a folate receptor alpha (FRα) vaccine administered with cyclophosphamide (CP), demonstrating excellent safety and immunogenicity. To simplify the vaccine strategy for ease of use, we report here the results of a randomized phase II trial evaluating a lower vaccine dose alongside the original dose, administered with or without CP pretreatment. Patients and Methods: Patients with triple-negative breast cancer who completed all systemic and local therapies were assigned to receive either low-dose (825 μg) or high-dose (2.5 mg) vaccine peptides plus GM-CSF in six 4-week cycles, with or without CP prior to vaccination. Safety was monitored, and immunogenicity was evaluated before and after vaccination. Results: A total of 80 patients were dosed with vaccine, and 58 patients were evaluable for immunogenicity. Vaccination was well tolerated and elicited immunity in 83% of patients. Levels of FRα-specific T cells were high, persistent, and comparable with T-cell levels against tetanus toxoid. No differences in immunity were observed between the two doses. CP pretreatment also did not affect the immune responses. Recurrences occurred in eight evaluable patients and were unrelated to the treatment arm. No patients died during the study because of their disease. Conclusions: The reduced-dose FRα vaccine is as effective as the original dose and does not require CP to generate maximal immunity. These findings may inform the design of trials testing efficacy in triple-negative breast cancer or other cancers.