Metabolic Reprogramming in Oral Cancer: A Narrative Review of Therapeutic Perspectives with Emphasis on Dichloroacetate.
Level 5 - mechanism / opinion, no new human data
Narrative review describing biological mechanisms without systematic methodology or primary clinical trial data.
PubMed 42510964 · doi:10.3390/cimb48070724
What was done
This narrative review synthesized evidence on metabolic reprogramming pathways in oral squamous cell carcinoma, examining the interplay among glycolysis, mitochondrial metabolism, glutamine metabolism, and fatty acid oxidation. It evaluated the therapeutic potential of dichloroacetate as an inhibitor of pyruvate dehydrogenase kinase, its translational barriers, and its potential synergy with paclitaxel.
What was found
The abstract reports no numerical findings or quantitative metrics. Mechanistically, oral squamous cell carcinoma exhibits metabolic plasticity where functionally active mitochondria operate alongside enhanced aerobic glycolysis. Dichloroacetate inhibits pyruvate dehydrogenase kinase and partially reverses the glycolytic phenotype by restoring mitochondrial glucose oxidation. Standalone efficacy is reported to be restricted by toxicity, pharmacokinetic constraints, and compensatory adaptations, while combination with paclitaxel is described to disrupt cytoskeletal integrity and metabolic homeostasis.
Why it matters
The review outlines how targeting mitochondrial metabolism with metabolic modulators could potentially sensitize treatment-resistant oral cancers to conventional chemotherapeutics like paclitaxel.
Limits
As a narrative review, the work lacks a systematic search protocol and reports no new empirical or human clinical data. The abstract provides no quantitative effect sizes, patient numbers, dosage parameters, or safety profiles. Clinical efficacy and safety in human patients remain unestablished.
Cited by
- supports Dichloroacetate (DCA) activates pyruvate dehydrogenase.