In a groundbreaking new study poised to reshape our understanding of diet and cancer progression, researchers have uncovered a disturbing link between the consumption of sugary drinks and the metastatic spread of colorectal cancer. This revelation not only deepens the biological understanding of how certain sugars influence malignancy but also highlights the molecular mechanisms that facilitate the deadly migration of cancer cells. Published in the esteemed journal Nature Metabolism, the research reveals how fructose and glucose—two simple sugars abundantly found in sweetened beverages—can fuel colorectal cancer metastasis through a hitherto underappreciated enzymatic pathway involving sorbitol dehydrogenase (SORD).
Colorectal cancer remains one of the most common and lethal cancers worldwide, with metastasis being the primary cause of cancer-related deaths. Despite advances in treatments, the complex biology underlying metastatic progression has remained elusive, with few lifestyle factors shown to directly influence metastatic dynamics. This seminal study, led by Feng, T., Luo, Q., Liu, Y., and colleagues, provides strong evidence that dietary sugars distinctively contribute to the aggressiveness of colorectal tumors once they are formed. It challenges previous assumptions that sugar consumption affects cancer solely through caloric intake or obesity-related mechanisms, shining a spotlight instead on specific biochemical pathways driven by sugar metabolites.
At the heart of the discovery is the enzyme sorbitol dehydrogenase (SORD), a catalyst responsible for converting sorbitol into fructose. Sorbitol, a sugar alcohol, is known to accumulate when glucose and fructose levels are high, particularly after ingestion of sugary beverages. The research team meticulously demonstrated how SORD acts as a metabolic switch within colorectal cancer cells, enabling them to harness fructose from the diet and convert it into energy and biomass required for metastatic spread. This metabolic adaptation empowers tumor cells to survive harsh conditions during migration and colonize distant organs more effectively.
Using advanced metabolomic profiling and in vivo models, the study uncovered that excess fructose and glucose intake dramatically increased intracellular sorbitol levels, which in turn elevated SORD activity. Enhanced SORD function fueled key downstream metabolic pathways, including glycolysis and the pentose phosphate pathway, critical for generating both ATP and nucleotides—the essential building blocks for cell division and survival during metastasis. When SORD expression was genetically silenced or pharmacologically inhibited, cancer cells displayed significantly impaired metastatic potential, underscoring SORD’s pivotal role as a metabolic driver.
Importantly, this research employed patient-derived colorectal cancer cells and analyzed clinical data to corroborate laboratory findings. Tumor samples from patients with high sugary drink intake exhibited elevated SORD expression and metabolic signatures consistent with fructose-driven pathways. Moreover, elevated SORD levels correlated with poorer prognosis and increased metastatic burden. This clinico-pathologic evidence not only validates the biological mechanism but also identifies SORD as a potential prognostic biomarker and therapeutic target.
Delving deeper into the cellular consequences, the authors described how fructose metabolism via SORD augmented the production of reactive oxygen species (ROS) and activated signaling cascades such as the MAPK and PI3K/AKT pathways. These molecular changes enhanced tumor cell motility, invasion, and resistance to apoptosis—hallmarks of metastatic aggressiveness. Intriguingly, fructose-derived metabolites also appeared to modulate the tumor microenvironment by influencing stromal cells and immune infiltrates, thereby creating a pre-metastatic niche conducive to cancer dissemination.
The implications of these findings are profound, calling into question public health messages regarding sugar consumption, especially since sweetened beverages are a major source of fructose and glucose worldwide. While the detrimental effects of excessive sugar on metabolic syndrome and obesity are well-documented, this study pinpoints a direct oncogenic consequence of acute sugar intake on cancer cell biology. It suggests that even beyond overall calorie count, the specific metabolic fate of sugars in cancer cells can dramatically alter disease progression.
Furthermore, this research offers a potential new therapeutic avenue. Inhibiting SORD activity pharmacologically could selectively disrupt fructose metabolism in cancer cells, starving them of critical resources needed for metastasis without broadly affecting normal tissues. Such targeted intervention might complement existing chemotherapy and immunotherapy regimens, particularly for patients with sugar-driven colorectal tumors. Early preclinical data demonstrated that SORD inhibitors significantly reduced metastatic lesions in mouse models without noticeable toxicity.
The study also poses urgent questions for future investigation. For instance, what is the extent to which dietary sugars influence other cancer types? Are there synergistic effects between sugar metabolism and genetic mutations commonly found in colorectal cancer? Could lifestyle interventions aimed at reducing sugary drink consumption be integrated with molecular diagnostics to personalize patient care? Addressing these queries could revolutionize cancer prevention and management strategies.
Beyond clinical implications, the study advances fundamental cancer metabolism knowledge. By elucidating the contextual role of SORD in fructose utilization, it refines metabolic paradigms in oncology, showcasing the versatility and adaptability of tumor cells in exploiting available nutrients. This aligns with the emerging appreciation of metabolism as a dynamic and targetable vulnerability in malignancy, moving beyond the conventional Warburg effect to encompass distinct sugar metabolic pathways.
In an era where dietary habits are in flux and sugary drinks remain globally consumed, this research acts as a clarion call for scientists, clinicians, and policymakers alike. It substantiates the biochemical basis for dietary recommendations and reinforces the necessity of controlling sugar intake to mitigate not only metabolic diseases but also cancer progression. Public awareness campaigns may now need to incorporate these oncological risks to more effectively curb the rising tide of sugar-linked health problems.
This pioneering study truly epitomizes the convergence of nutritional science, molecular biology, and clinical oncology, yielding insights with far-reaching ramifications. It exemplifies how molecular dissection of diet-derived metabolites can reveal unexpected and crucial nodes in cancer pathogenesis. With colorectal cancer being a leading cause of mortality, the identification of SORD as a metabolic linchpin offers tangible hope for new interventions that could enhance survival and quality of life for affected patients.
As the research community digests these findings, there is cautious optimism that SORD-targeted strategies may soon enter the clinical trial phase. Coupled with lifestyle modification, such targeted therapies could transform colorectal cancer treatment paradigms. The meticulous work by Feng and colleagues not only enriches cancer science but also underscores the intricate interplay between diet and disease, highlighting sugar’s dark side in cancer metastasis.
In summary, this comprehensive investigation into the metabolic ramifications of fructose and glucose from sugary drinks uncovers a critical enzymatic driver—SORD—that significantly enhances colorectal cancer metastasis. Through detailed biochemical analyses, patient validation, and experimental inhibition studies, the research delineates a novel metabolic vulnerability that holds promise for improved prognostics and therapeutics. The study compellingly illustrates how seemingly innocuous dietary components can profoundly influence cancer biology, redefining how we approach cancer prevention and treatment in the 21st century.
Article Title:
Fructose and glucose from sugary drinks enhance colorectal cancer metastasis via SORD
Article References:
Feng, T., Luo, Q., Liu, Y. et al. Fructose and glucose from sugary drinks enhance colorectal cancer metastasis via SORD. Nat Metab (2025). https://doi.org/10.1038/s42255-025-01368-w
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