Experimental cancer treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Contents

* 1 Overview
* 2 Angiostatic-based treatments
* 3 Dichloroacetate (DCA) Treatment
* 4 Bacterial treatments
* 5 Gene therapy
* 6 Telomerase therapy
* 7 Thermotherapy
* 8 Complementary and alternative cancer treatment
* 9 Controversial therapies
* 9.1 Diet therapy
* 9.2 Insulin potentiation therapy
* 10 References
* 11 Resources

## Overview

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Experimental cancer treatments are medical therapies intended or claimed to treat cancer (see also tumor) by improving on, supplementing or replacing conventional methods (surgery, chemotherapy, radiation, and immunotherapy).

The entries listed below vary between theoretical therapies to unproven controversial therapies. Many of these treatments are alleged to only help against specific forms of cancer. It is not a list of treatments widely available at hospitals.

## Angiostatic-based treatments

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Every solid tumor (in contrast to liquid tumors like leukemia) needs to generate blood vessels to keep it alive once it reaches a certain size. Usually, blood vessels are not built elsewhere in an adult body unless tissue repair is actively in process. The anti-angiogenesis (angiostatic) agent endostatin and related chemicals can suppress the building of blood vessels, preventing the cancer from growing indefinitely. In tests with patients, the tumor became inactive and stayed that way even after the endostatin treatment was finished. The treatment has very few side effects but appears to have very limited selectivity. Other angiostatic agents like thalidomide and natural plant-based substances are being actively investigated.

## Dichloroacetate (DCA) Treatment

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Cancer cells generally use glycolysis rather than oxidation for energy (the Warburg effect), as a result of hypoxia in tumors and damaged mitochondria.[1] The body often kills damaged cells by apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells.

A study published in January 2007 by researchers at the University of Alberta,[2] testing DCA on in vitro cancer cell lines and a rat model, found that DCA restored mitochondrial function, thus restoring apoptosis, killing cancer cells in vitro, and shrinking the tumors in the rats.[3]

## Bacterial treatments

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Chemotherapeutic drugs have a hard time penetrating tumors to kill them at their core because these cells may lack a good blood supply. Researchers have been using anaerobic bacteria, such as Clostridium novyi, to consume the interior of oxygen-poor tumours. These should then die when they come in contact with the tumour's oxygenated sides, meaning they would be harmless to the rest of the body. A major problem has been that bacteria don't consume all parts of the malignant tissue. However combining the therapy with chemotheraputic treatments can help to solve this problem. Another strategy is to use anaerobic bacteria that have been transformed with an enzyme that can convert a non-toxic prodrug into a toxic drug. With the proliferation of the bacteria in the necrotic and hypoxic areas of the tumour the enzyme is expressed solely in the tumour. Thus a systemically applied prodrug is metabolised to the toxic drug only in the tumour. This has been demonstrated to be effective with the non pathogenic anaerobe Clostridium sporogenes.

## Gene therapy

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Introduction of tumor suppressor genes into rapidly dividing cells has been thought to slow down or arrest tumor growth. Another use of gene therapy is the introduction of enzymes into these cells that make them susceptible to particular chemotherapy agents; studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage.

## Telomerase therapy

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Because most malignant cells rely on the activity of the protein telomerase for their immortality, it has been proposed that a drug which inactivates telomerase might be effective against a broad spectrum of malignancies. At the same time, most healthy tissues in the body express little if any telomerase, and would function normally in its absence.

A number of research groups have experimented with the use of telomerase inhibitors in animal models, and as of 2005 and 2006 phase I and II human clinical trials are underway. Geron Corporation, is currently conducting two clinical trials involving telomerase inhibitors. One uses a vaccine (GRNVAC1) and the other uses a lipidated drug (GRN163L).

## Thermotherapy

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Localized application of heat has been proposed as a technique for the treatment of malignant tumours. Intense heating will cause denaturation and coagulation of cellular proteins, rapidly killing cells within a tumour.

More prolonged moderate heating to temperatures just a few degrees above normal can cause more subtle changes. A mild heat treatment combined with other stresses can cause cell death by apoptosis. There are many biochemical consequences to the heat shock response within in cell, including slowed cell division and increased sensitivity to ionizing radiation therapy.

There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound (FUS or HIFU), microwave heating, induction heating, or direct application of heat through the use of heated saline pumped through catheters. Experiments have been done with carbon nanotubes that selectively bind to cancer cells. Lasers are then used that pass harmlessly through the body, but heat the nanotubes, causing the death of the cancer cells. Similar results have also been achieved with other types of nanoparticles including gold-coated nanoshells and nanorods which exhibit certain degrees of 'tunability' of the absorption properties of the nanoparticles to the wavelength of light for irradiation. The success of this approach to cancer treatment rests on the existence of an 'optical window' in which biological tissue (i.e,. healthy cells) are completely transparent at the wavelength of the laser light while nanoparticles are highly absorbing at the same wavelength. Such a 'window' exists in the so-called near infrared region of the electromagnetic spectrum. In this way, the laser light can pass through the system without harming healthy tissue and only diseased cells, where the nanoparticles reside, get hot and are killed.

One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. A great deal of current research focuses on precisely positioning heat delivery devices (catheters, microwave and ultrasound applicators, etc.) using ultrasound or magnetic resonance imaging, as well as of developing new types of nanoparticles that make them particularly efficient absorbers while offering little or no concerns about toxicity to the circulation system. Clinicians also hope to use advanced imaging techniques to monitor heat treatments in real time--heat-induced changes in tissue are sometimes perceptible using these imaging instruments.

See also Photothermal Therapy.

## Complementary and alternative cancer treatment

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See main article: Alternative medicine

In the year 2000, the American Cancer Society published American Cancer Society's Guide to Complementary and Alternative Cancer Methods. There are over 200 substances and therapies in this book, and while there is a varying degree of success with each of the methods, it appears that some of the techniques will work at times, however no technique will work in all situations, which, practitioners claim, is similar to the success rate of conventional techniques. Many of these treatments are similar to ancient ways of dealing with disease. According to practitioners of such techniques, various options are available to anyone who wants this information, however, they caution that discretion is advised no matter what methods a person chooses to pursue.

Produced in collaboration with the American Cancer Society (ACS), NCCN Treatment Guidelines for Patients provide cost-free, specific, and understandable information that patients and their families can use to make timely and well-informed decisions about cancer treatment. Developed from the NCCN Clinical Practice Guidelines in Oncology™, the patient versions of the guidelines describe diagnosis and treatment of frequently occurring cancers and supportive care issues in an easy-to-read format. These guidelines provide patients access to the same decision pathways their oncologists use.

## Controversial therapies

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### Diet therapy

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In the late 1940s, German-born physician Dr. Max Gerson proposed a therapy claimed to be successful in the treatment of advanced cancer, normalizing metabolism and helping the body's immune system act on cancer cells. It is a high potassium, low sodium (saltless) diet, with no fats or oils, and high in fresh raw fruits and vegetables and their juices. (See for instance the lecture [2], and the book A Cancer Therapy: Results of Fifty Cases, by Max Gerson, M.D.) (ISBN 0-9611526-2-1). Other scientists give credence to published accounts of such treatments to suppress the growth rate of cancer, despite general disagreement on the underlying mechanisms: http://www.krysalis.net/cancer4.htm

As with Max Gerson, Johanna Budwig proposed another diet therapy claimed to treat cancer. Most oncologists have a belief that a diet alone cannot treat cancer. Reports of dramatic remissions as a result of the Budwig diet are anecdotal, and not supported by peer-reviewed research. (On the other hand, her diet is good from a nutritional point of view to counteract some side-effects of other treatments.) Some basic research on flax oil (preferred by Budwig) is available: [3] [4] [5] [6] [7]

### Insulin potentiation therapy

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In insulin potentiation therapy (IPT), insulin is given in conjunction with low-dose chemotherapy. Its proponents claim insulin therapy increases the uptake of chemotherapeutic drugs by malignant cells, permitting the use of lower total drug doses and reducing side effects.

Some In vitro studies have demonstrated the principle of IPT [8][9] .

The first clinical trial of IPT for treating breast cancer was done in Uruguay and published in 2003/2004. Insulin combined with low-dose methotrexate (a chemotherapy drug) resulted in greatly increased stable disease, and much reduced progressive disease, compared with insulin or low-dose methotrexate alone. Although the study was very small (30 women, 10 per group), the results appear to be very promising. [10]

## References

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1. ↑ Xu R, Pelicano H, Zhou Y, Carew J, Feng L, Bhalla K, Keating M, Huang P (2005). "Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia". Cancer Res. 65 (2): 613–21. PMID 15695406.CS1 maint: Multiple names: authors list (link)
2. ↑ depmed.ualberta.ca
3. ↑ Bonnet S, Archer S, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee C, Lopaschuk G, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter C, Andrade M, Thebaud B, Michelakis E (2007). "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth". Cancer Cell. 11 (1): 37–51. PMID 17222789.CS1 maint: Multiple names: authors list (link)

## Resources

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* American Cancer Society

* National Cancer Institute

* Dichloroacetate (DCA) Research

* Nature Reviews Cancer website

* Audio-video Physician Interviews on Cancer Treatment Breakthroughs

* "Questionable Cancer Therapies"

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