Evidence map›Paper›PMID 27993896›Full record

ReviewCarcinogenesis2017

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

Iñigo San-Millán, George A Brooks

Registry-linked trialOpen access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03221920 (Effect of Very Low Carbohydrate Diet to Glasgow Prognostic Score, Serum Lactate and TNF Alpha on Colorectal Cancer Patients With Best Supportive Care), which is not on this map. Cited by 378 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
378citing papers in PubMed, 3 pooled it
16.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03221920 naunknown statusnot on this map

Effect of Very Low Carbohydrate Diet to Glasgow Prognostic Score, Serum Lactate and TNF Alpha on Colorectal Cancer Patients With Best Supportive Care

TypeinterventionalSponsorDr. Soetomo General HospitalRan2017 to 2017Enrolled26ConditionsDiet Modification, Colorectal Adenocarcinoma, Systemic Inflammation, TNF AlphaArmsVery Low Carbohydrate Diet
3 · Its place in the literature

Who cites it

378 citing papers in PubMed, 3 syntheses or guidelines pooled it, 596 citations in OpenAlex.

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  8. Lactate, Carbohydrate Restriction, and Cancer Metabolism.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026
    Review
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318 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Iñigo San-MillánDepartment of Physical Medicine and Rehabilitation, University of Colorado School of Medicine, Aurora, CO 80045, USA.
George A BrooksDepartment of Integrative Biology, University of California, Berkeley, CA 94720, USA.
University of California, Berkeley · USUniversity of Colorado Denver · US

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Wendy M Kohrt · 1995 to 2026
$32.6M
6 · The paper itself

Abstract

Herein, we use lessons learned in exercise physiology and metabolism to propose that augmented lactate production ('lactagenesis'), initiated by gene mutations, is the reason and purpose of the Warburg Effect and that dysregulated lactate metabolism and signaling are the key elements in carcinogenesis. Lactate-producing ('lactagenic') cancer cells are characterized by increased aerobic glycolysis and excessive lactate formation, a phenomenon described by Otto Warburg 93 years ago, which still remains unexplained. After a hiatus of several decades, interest in lactate as a player in cancer has been renewed. In normal physiology, lactate, the obligatory product of glycolysis, is an important metabolic fuel energy source, the most important gluconeogenic precursor, and a signaling molecule (i.e. a 'lactormone') with major regulatory properties. In lactagenic cancers, oncogenes and tumor suppressor mutations behave in a highly orchestrated manner, apparently with the purpose of increasing glucose utilization for lactagenesis purposes and lactate exchange between, within and among cells. Five main steps are identified (i) increased glucose uptake, (ii) increased glycolytic enzyme expression and activity, (iii) decreased mitochondrial function, (iv) increased lactate production, accumulation and release and (v) upregulation of monocarboxylate transporters MTC1 and MCT4 for lactate exchange. Lactate is probably the only metabolic compound involved and necessary in all main sequela for carcinogenesis, specifically: angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism. We hypothesize that lactagenesis for carcinogenesis is the explanation and purpose of the Warburg Effect. Accordingly, therapies to limit lactate exchange and signaling within and among cancer cells should be priorities for discovery.

Indexed as

CarcinogenesisGlycolysisHumansLactic AcidMitochondriaNeoplasmsNeovascularization, PathologicOxidative StressLactic Acid

Identifiers

PMID27993896
PMCPMC5862360
OpenAlexW2562182278

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.