Blocking Cancer’s Fuel Source

Cancer is a complex disease involving numerous changes in cell physiology including the metabolic process on how it may be fed. It is defined as cells that are undergoing rapid replication thereby needing a constant source of both energy and byproducts for cell creation.

Looking for genetic variants (or defects) on genes that are responsible for tumor suppression as well as genes that may give a cancer cell more direct access to fuel sources may be important steps to help understand the disease and limit growth. The decreased expression of tumor suppressor genes, our genomic “watchman” involved in sensing and stopping aberrant cell replication, is a part of the problem that may allow cancer to manifest. A better understanding of these genes and learning ways to manipulate their expression is key.

Cancer & Glycolysis

Cancer needs a fuel source, or a supply line. All cells make energy through glucose metabolism but cancer seems to require greater amounts. A process known as aerobic glycolysis or the Warburg effect [3] is a robust metabolic hallmark of most tumors. Normal cells make energy through a process taking glucose (sugar) through a metabolic chain called glycolysis that makes a chemical called pyruvate. Pyruvate then converts to another chemical in the mitochondria (powerhouse) of the cell to enter a process that produces a lot of energy, the goal of glucose metabolism. Cancer cells are different. They can force pyruvate down a different pathway making high quantities of lactic acid in the cytoplasm (the belly) of the cell. There, lactate ferments forming an acid environment and more fuel for cell replication; but it isn’t a very efficient system. So, why do cancer cells do this?

The belief has been that cancer cells may have damaged mitochondria that don’t allow pyruvate to enter to make energy the way normal cells do. However, recent studies have shown that, though cancer cells need energy for replication, they also need other components [2]. Much like a factory creating shoes might need energy to run the machines; it also needs leather, rubber and laces. Since cancer cells gobble up glucose through various pathways [3], their need for it goes beyond simple energy production.

Glucose can enter other metabolic pathways to make other components (leather, rubber, and laces). Ultimately, the Warburg Effect supports a metabolic environment that allows for rapid biosynthesis of both energy and materials to support growth and proliferation of new cells in cancer.

Although there is no specific gene mutation common to all cancers, nearly all cancers express aerobic glycolysis (the Warburg Effect) as discussed above, regardless of their tissue or cellular origin. Genes for glycolysis are over-expressed and genes that make enzymes to convert pyruvate to acetyl co-A in the mitochondria as well as those that help get pyruvate into the mitochondria may be under-expressed. Therefore, it might behoove us to look at such genes in cancer patients [5].

Every metabolic process is under the control of genetic factors making enzymes to initiate action. Since cancer may be fueled through excess lactic acid formed when pyruvate fails to take its normal path, would those individuals with variants on the genes responsible to move pyruvate normally into healthy energy production be more susceptible to cancer? Would a patient with cancer be more apt to express defects on genes that might lead to accelerate production of a fuel source preferred by cancer cells? Could we, by assessing such variants in a patient’s genes help formulate a plan to help ‘cut-off’ necessary supply lines? These are the questions only time and trials may answer but ones that I feel are worthy to explore.

Some of the genes in question are the HIF1A, PDH, LDH, KRAS, and PTEN genes. All have been proven to play a part in excess lactic acid production [6]. For instance, the PDH gene, most directly responsible to converting pyruvate to acetyl co A, may be down regulated with genetic variants expressed. Its function is directly hindered by excess HIF-1A expression as well as exogenous sources of toxins suggesting other environmental influences can also be involved. Those with PDH and HIF defects may be more apt to create access lactic acid, a fuel source for cancer. Dietary considerations in such individuals might be to restrict upstream nutrients that feed that pathway – namely glucose.

In summary, healthy cells take glucose through a process called glycolysis to make pyruvate. This makes some energy necessary for cell function. Pyruvate, through enzymes produced by specific genes (HIF & PDH), then converts to acetyl co-A to make much more energy for normal cell health. If one has variants on the genes responsible for such conversions, has variants on genes responsible to aide lactic acid’s ability to enter the mitochondria inside the cell, or lacks supportive substrates necessary to convert pyruvate to acetyl co-A regardless of gene expression, the cell makes excess lactic acid, a known fuel for cancer. Increase fuel equals increased growth.

Our hope is that by better understanding specific metabolic pathways, the genes that drive them, as well as cofactors influencing flow, we can better formulate both a nutritional and dietary plan to help cancer patients. For more information on specific genetic testing, one may contact Conners Clinic at


  1. Cancer is a preventable disease that requires major lifestyle chages. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, et al. Pharm Res 2008, 25:2097-2116
  2. Cancer Undefeated. Bailar JC, Gornik HL; N Engl J Med 1997, 336:1569-1574
  3. Buzzai, M., Bauer, D.E., Jones, R.G., Deberardinis, R.J., Hatzivassiliou, G., Elstrom, R.L., and Thompson, C.B. Oncogene. 2005; 24: 4165–4173
  4. The Warburg Effect: How Does it Benefit Cancer Cells?

Maria V. Liberti, et al

  1. New guardians of the genome. Roth DB, Gellert M; Nature 2000, 404:823-825
  2. Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

Patrick S. Ward, Craig B. Thompson. Cancer Cell, Volume 21, Issue 3, p297–308, 20 March 2012


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