Boosting Cancer Treatment via Diet and Metabolic Interventions
A recent study from the Journal Cell examines the influence of a glycolytic metabolite, specifically methylglyoxal (MGO), in relation to BRCA2 gene mutation and its broader implications in tumor suppression. Below is a summarized outline with preventative implications and future prospects for medical therapies.
Summary and Key Points:
Methylglyoxal’s Role:
MGO, a by-product of glycolysis, induces genome-wide single base substitution (SBS) mutations particularly in cells with a monoallelic mutation of the BRCA2 gene.
Bypassing the "Two-Hit" Hypothesis:
Typically, both alleles of a tumor suppressor gene must be inactivated for cancer to develop (Knudson’s two-hit hypothesis). However, MGO can transiently inactivate BRCA2 function, effectively bypassing the need for a second genetic "hit."
Link to Metabolic Changes:
Oncogenic changes or shifts in metabolic pathways that increase MGO production can initiate similar genetic events, tying together metabolic reprogramming, metabolic disorders, and dietary factors with cancer initiation.
Implications for Medical Therapies:
Targeting MGO:
Therapeutic strategies could focus on modulating MGO levels or its pathways to protect BRCA2 functionality in patients with a predisposition to mutations.
Dietary Interventions:
Understanding the impact of dietary components that influence glycolysis and MGO production may lead to dietary recommendations or interventions that could mitigate cancer risk in susceptible populations.
Predictive Biomarkers:
MGO levels could potentially serve as biomarkers for assessing cancer risk or the effectiveness of interventions aimed at reducing tumor initiation through metabolic pathways.
Ketogenic Diet and Cancer Prevention
Reduction in Glycolysis:
A ketogenic diet could potentially reduce the availability of glucose, thus limiting the substrate for glycolysis and subsequently the production of harmful by-products like MGO.
Lower Insulin and IGF-1:
By reducing insulin and IGF-1 levels, which are involved in cancer cell proliferation, a ketogenic diet might further decrease cancer initiation and progression risks.
Influence on Metabolic Pathways:
Altering the body’s primary metabolic pathways from glucose utilization to ketone body metabolism may provide less favorable conditions for cancer cells, which prefer glucose for growth.
Reference:
Kong, Li Ren et al. “A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2.” Cell vol. 187,9 (2024): 2269-2287.e16. https://doi.org/10.1016/j.cell.2024.03.006
