Fighting Cancer with Bacteria
There are three unique ways that bacteria have been used to help fight cancer: they have been used as probiotics to help prevent cancer, they have been introduced into patients on purpose in order to elicit a fever (heat + immune) response, and (very recently) they have been used as a vehicle for cancer drug delivery.
A. Bacteria as probiotics against cancer
Lactic acid bacteria (LAB) are the most common type of bacteria used as probiotics; they are present in bacteria-treated foods that we eat such as yogurt. The lactic acid bacteria covert the foods’ complex sugars into lactic acid, generating the characteristic sour taste of fermented dairy foods.
Several studies have shown that milk fermented by LAB may show beneficial effects for preventing colon cancer and breast cancer (1). Animals studies have shown that lactice acid bacteria can help protect against colon cancer in rodents, and human epidemiological studies have confirmed lower rates of colon cancer in populations who consume higher amounts of fermented dairy products as part of their staple diet.
The mechanism of action for these probiotics reducing cancer risk is not well understood, but several hypotheses exist, including:
1. Probiolotics may exert anti-carcinogenic effects by decreasing the activity pro-cancerous enzymes. For instance, lactic acid bacteria might exert anti-mutagenic effects by binding with (and inactivating) heterocyclic amines (carcinogenic substances formed in cooked meat).
2. Probiotics’ lowering of food pH (via lactic acid secretion) reduces the chances of other organisms (“bad bacteria”) growing and spoiling food. The corresponding decrease in gastrointestinal infections may also decrease risk of cellular aggravations and tumor development.
3. Probiotics may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine. (e.g., lactic acid bacteria inhibit beta-glucuronidase, an enzyme which generates carcinogens in the digestive system.)
4. Probiotics may protect the detoxification function of the kidney and liver.
5. Probiotics may aid in adaptation to smoke irritation generated during cooking, heating and/or tobacco smoking (possibly by restoring natural killer cell activity which is lowered in smokers). Smoking is the most important lifestyle risk factor for bladder cancer, and epidiomiological evidence shows that consumption of probiotic foods reduces the risk of this specific type of cancer in humans. (4)
6. Probiotics stimulate mucosal INF-gamma (a cytokine) secretion to stimulate immune protection and enhance apoptosis, reducing cancer risk. Evidence suggests that probiotics may regulate this cytokine secretion to ensure optimal protection with minimal damage to health cells (2).
B. Cancer Fever Therapy
In the early 1900’s, Dr. William B. Coley, chief of the Bone Service at what is now Memorial Sloan Kettering Cancer Center, purposely infected his cancer patients with Streptococcus pyogenes and Serratia marcescens to induce a fever response. Ancient writings suggest that the Egyptian priest/physician Imhotep infected tumors before surgically removing them, and in the 13th century, an Italian saint was reputed to have his tumor-afflicted leg miraculously healed shortly after the malignant growth burst through the skin and became infected. While we find the concept of intentionally infecting any patient as appalling, it was not uncommon for physicians in the 18th and 19th centuries to apply septic dressings to ulcerated tumors or to deliberately introduce infections such as erysipelas, gangrene, or syphilis as part of their treatment regimen.
The aim of these therapies was generate a high fever in cancer patients through a severe case of bacterial infection. Although quite antiquated, the concept of fever therapy for cancer has formed the rationale and foundation for modern cancer immunotherapies and hyperthermia treatments (which seek to replicate the effects of a fever response in fighting cancer without having to infect a patient with potentially dangerous/lethal bacteria).
C. Bacteria as vehicles for drug and gene delivery.
Bacteria can be engineered to generate therapeutic payloads of anti-cancer drugs or gene products that help combat cancer. These engineered bacteria possess many benefits over current cancer therapies, which are often highly toxic, poorly penetrate tumor tissue, and ineffectual at targeting tumors. Genetically engineered bacteria can be made to possess similar characteristics as the bacteria that naturally live inside one’s body (e.g., the billions of bacteria in the intestines). These bacteria will localize to their “natural habitat” and locally produce anti-cancer products in that location.
Other examples of bacterial localization (to tumor) mechanisms include: specific chemotaxis, preferred growth, and hypoxic germination (tumor possess certain chemical signatures, grow much faster than regular cells, and have hypoxic cores). St Jean et al. have reported that, “deleting the ribose/galactose chemoreceptor has been shown to cause bacterial accumulation in therapeutically resistant tumor regions” (3).
Mechanisms-of-action for engineered bacteria once they arrive at the site of the tumor include: (temporally controlled) cytotoxin release, enzymatic activation of pro-drugs (making them active only at the site of the tumor), and secretion of physiologically active biomolecules. To date, bacteria have been engineered to express the anti-tumor products: tumor-necrosis-factor-alpha, hypoxia-inducible-factor-1-alpha antibodies, interleukin-2, and cytosine deaminase. (3)
(Note: this use of bacteria to help in the fight against cancer is a direct application of engineered bacteria into a patient’s body. It is distinct from the concept “bacteria factories” used to mass-produce cancer drugs like taxol (which at one point in time could only be harvested from the yew tree). “Factory” bacteria never enter a patient and I do not consider them a “bacterial treatment for cancer” as the topics discussed above are.)
(1) de Moreno de LeBlanc et al. 2007 (de Moreno de LeBlanc A, Matar C, Perdign G. “The application of probiotics in cancer.” Br J Nutr. 2007 Oct;98 Suppl 1:S105-10.)
(2) Clancy and Pang 2007 (Clancy RL, Pang GJ. “Probiotics-industry myth or a practical reality?” Am Coll Nutr. 2007 Dec;26(6):691S-4S.)
(3) St Jean et al. 2008 (St Jean AT, Zhang M, Forbes NS. “Bacterial therapies: completing the cancer treatment toolbox.” Curr Opin Biotechnol. 2008 Oct;19(5):511-7. Epub 2008 Sep 18.)
(4) Hozyasz 2008 (Hozyasz KK. “Promising role of probiotics in prevention of smoking-related diseases” [Article in Polish] Przegl Lek. 2008;65(10):706-8.)