THE MOSS REPORTS

Last week I began a two-part discussion of new developments in the field of photodynamic therapy (PDT). The discussion concludes, with references and resources, this week.

At present, PDT is FDA-approved for use in the treatment of a few, mainly early stage, cancers. However, as research progresses and more and more ingenious methods of selectively targeting cancer tissue are developed, it is to be hoped that this minimally invasive treatment technique will come to occupy a more prominent place in the treatment of cancers of many kinds.

For thirty years I have been writing about cancer research and treatment. The fruit of my long career in this field is The Moss Reports, a comprehensive library of more than two hundred individual reports on specific cancer diagnoses. For a cancer patient, a Moss Report represents an invaluable guide and handbook for the journey ahead.

If you would like to order a Moss Report for yourself or someone you love, you can do so from our website, www.cancerdecisions.com, or by calling Diane at 1-800-980-1234 (814-238-3367 from outside the US).

We look forward to helping you.

SOME PROMISING NEW DEVELOPMENTS IN PDT, PART II

Most current methods of PDT work by generating highly energized oxygen molecules (called 'singlet oxygen') when the photosensitizer is activated by the light source. However, a team led by Dr. Karen Brewer of Virginia Tech University has developed a series of photosensitizing agents that are oxygen independent. Dr. Brewer's team is working with cell cultures to compare the effectiveness of the agents in the dark and in visible light. The team presented its findings at the 228th American Chemical Society National Meeting in Philadelphia in late August, 2004.

"Another improvement for our systems is that the agents are activated by visible light, as opposed to UV (ultraviolet) light," said Brewer, associate professor of chemistry. "Using only visible light is a safeguard against inadvertent damage of tissue."

The researchers have obtained results in three separate areas that, when used together, may provide more effective, less invasive, and more specific treatments for cancer and other diseases. In particular, they have developed some new tri-metallic 'supra-molecules' that can be introduced not just into cancer tissue in general, but into specific parts – called 'organelles' - of cancer cells themselves. The supra-molecules can then be activated by a specific wavelength of light that propagates efficiently through tissue. Only when the light hits these supra-molecules do they become toxic to the cancer cells.

The new system "allows much lower dosages of light to be effective, so we can use agents that are more aggressive and not get the side effects of chemotherapy," Prof. Brewer said. Researchers in her laboratory developed the new mixed-metal supra-molecular complexes that she and a colleague, Prof. Brenda Winkel, have proven are capable of breaking up DNA when activated by light (a process called 'photocleaving'). The researchers can also alter the wavelength of light that is used. "We can fine tune the compound for light-absorbing characteristics," said Prof. Brewer. "By using a lower energy [i.e., a higher wavelength of light, ed.] we can better penetrate the body."

Prof. Brian Storrie and Dr. Maria Teresa Tarrago-Trani of Virginia Tech's biochemistry department have developed what they call a 'rocket' mechanism, by which to deliver the cancer-killing agents to particular organelles. "We have used a polypeptide that binds to a cell surface receptor, and that molecule is over-expressed for certain cancers. We can deliver photosensitizers accurately to the cancer," Storrie said.

The delivery vehicle is actually the B-fragment of the shiga toxin, which is produced by the microbe that causes a form of dysentery (Shigella dysenteriae) as well as by certain disease-causing strains of E. coli. This may sound dangerous. However, while the shiga A-fragment is toxic, the B-fragment is not, and B-fragment therefore makes a harmless delivery system.

Professor Storrie developed the technique of using the B-fragment to deliver the photodynamic agents developed by Brewer directly into the cells (Harris 2002). This allowed the researchers to target particular cancer cells that have receptors for the B-fragment and to deliver the agent to the exact spot in the cell that enables the supra-molecule to attack it, thereby opening the way for the selective destruction of many crucial parts within cancerous cells.

"We can attach the delivery vehicles, change the light we need, change the biological target in the cells, and design a molecule that reacts with that part," said Prof. Brewer. She hopes that someday this system will be the basis for important strides in the treatment of cancer and other diseases.

Some Practical Applications

Photodynamic therapy is a highly promising treatment modality that has so far remained very much at the fringes of cancer treatment, overshadowed by the prevailing preference for chemotherapy. Because of this 'poor relation' status, research into PDT has historically been plagued by many obstacles and false starts. However, it now appears to be getting some of the serious scientific consideration that it deserves.

PDT has great potential as a way of killing cancer cells with less damage to normal tissues. For skin and superficial tumors, PDT can be administered using an external light source such as a laser attuned to the absorbency peak of the corresponding photosensitizer and delivered in a highly targeted way. In the case of deep-seated tumors, however, the light source generally must be applied (1) endoscopically (i.e., by inserting a tube into a hollow organ such as the esophagus) or intra-arterially, by way of a catheter threaded through the blood vessels to a target organ; (2) interstitially (i.e., by inserting a probe directly into a solid tissue, such as the liver); or (3) intraoperatively (i.e., in the course of surgery).

In such ways, PDT may be used in the treatment of larger internal areas, including the pleura (lining of the chest cavity) and peritoneum (lining of the abdominal cavity). Logically, it could be eventually be used in the treatment of many, if not most, kinds of cancer.

But caution is advised. PDT is certainly no cure-all. It has not been demonstrated, for instance, that PDT can be used with any external light source to treat advanced, systemic disease (Moss 2003). PDT may also be accompanied by more adverse effects than one might suppose by reading enthusiastic reports in the media or even in the scientific literature.

Because of this, readers who are interested in receiving PDT are urged to concentrate exclusively on those programs that use FDA or EU-approved agents, or that enroll patients in carefully designed clinical trials under institutional review board (IRB) supervision. This is important in order to safeguard the interests and rights of patients undergoing treatment with what remains a largely experimental treatment modality.

DEPARTMENT OF CORRECTIONS

In last week's newsletter I mistakenly referred to the metal rhodium as being liquid at room temperature, like mercury. This is incorrect. Rhodium is solid at room temperature. I apologize for this error.

Resources:

Here is contact information on some prominent centers using PDT:

Photodynamic Therapy Center
Roswell Park Cancer Institute
Elm & Carlton Streets
Buffalo, NY 14263 USA
1-800-ROSWELLPDT Nurse = (716) 845-4427
email: pdtctr@roswellpark.org
http://www.roswellpark.org/document_187_620.html

Photodynamic Therapy Center
Department of Radiation Oncology
The Brody School of Medicine at East Carolina University
Greenville, NC 27858
Phone 1-800-223-9328 (252) 744-2900 / Fax (252) 744-2812
http://www.ecu.edu/radiationoncology/PDT/default.htm

Mr. Colin Hopper
Eastman Dental Institute for Oral Health Care Sciences
University College London
256 Gray's Inn Road,
London WC1X 8LD, UK
Fax: +44 (0) 20 7915 1056
Email: c.hopper@eastman.ucl.ac.uk

PDT Treatment in China: http://www.pdt-med.com/en/treatment.htm

Prof. Morrison: http://www.chem.purdue.edu/morrison/
Karen Brewer 540-231-6579, kbrewer@vt.edu,
Brian Storrie 540-231-6434, storrie@vt.edu,
Ken Meissner 540-231-2512, cmeissne@vt.edu
Sally Harris 540-231-6759 slharris@vt.edu

Prof. Avigdor Scherz, MD, PhD
Head-Minerva-Avron Center for Photosynthesis
Department of Plant Sciences
Weizmann Institute of Science, Rehovot, 76100
e-mail: Avigdor.Scherz@weizmann.ac.il
Tel(O): +972-8-9344309
Tel(H): +972-8-9473943
Fax: +972-8-9344181

References:

[Anonymous]. Light turns on anticancer agents. Cancerfacts.com. August 29, 2004. Retrieved September 1, 2004 from:
http://www.cancerfacts.com/Home_News.asp?NewsId=1717&CB=14&CancerTypeId=4

Boutin, Chad. Bright idea could doom cancer and viruses, say Purdue scientists. August 23, 2004. Purdue University Press Release. Retrieved September 1, 2004 from:
http://www.chem.purdue.edu/NewsFeed/newsstory.asp?itemID=121

Harris, Sally. Researchers develop exciting new arsenal in war against cancer. December 11, 2002. Retrieved September 1, 2004 from:
http://www.technews.vt.edu/Archives/2002/Dec/02211.htm

Holder AA, Swavey S, Brewer KJ. Design aspects for the development of mixed-metal supramolecular complexes capable of visible light induced photocleavage of DNA. Inorg. Chem. 2004;43:303-308.

Menon EL, Perera R, Navarro M, Kuhn RJ, Morrison H. Phototoxicity against tumor cells and Sindbis virus by an octahedral rhodium bisbipyridyl complex and evidence for the genome as a target in viral photoinactivation. Inorg. Chem. 2004;43:5373-81.

Moss, RW. Patient responses to Cytoluminescent Therapy for cancer: an investigative report of early experiences and adverse effects of an unconventional form of photodynamic therapy. Integr Cancer Ther. 2003;2:371-89.

IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.

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