Iñigo San-Millán · Carcinogenesis 2016 · theoretical framework / hypothesis paper · n=?

Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect

Cited 612 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Mechanism-based reasoning and theoretical hypothesis paper with no empirical human data.

OpenAlex W2562182278 · doi:10.1093/carcin/bgw127 · record verified 2026-08-26

What was done

This conceptual paper applied principles from exercise physiology and metabolic signaling to formulate a mechanistic hypothesis regarding the role of lactate in cancer. It outlines a theoretical framework ('lactagenesis') to explain the functional purpose of the Warburg effect in driving carcinogenesis.

What was found

The abstract reports a conceptual model and contains no quantitative experimental numbers or empirical data. The authors propose a five-step sequence in lactagenic cancer cells: increased glucose uptake, increased glycolytic enzyme expression/activity, decreased mitochondrial function, increased lactate production and release, and upregulation of monocarboxylate transporters (MCT1 and MCT4). They hypothesize that lactate acts as an essential signaling molecule promoting angiogenesis, immune escape, cell migration, and metastasis.

Why it matters

The paper frames lactate not as an inert waste product of aerobic glycolysis, but as an active signaling driver of cancer progression, suggesting monocarboxylate transporters and lactate signaling pathways as key therapeutic targets.

Limits

The publication is purely theoretical and provides no original in vitro, in vivo, or clinical experimental data. Proposed mechanisms and therapeutic implications rely on theoretical synthesis rather than tested empirical interventions.

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