Latest developments in Phoyodynamic Therapy, or PDT
The momentum behind PhotoDynamic Therapy, or PDT, as a cancer treatment has been growing rapidly with new agents, new energy systems and results that put chemotherapy in the shade on cancers from glioma (GBM) to prostate cancer and Triple Negative Breast Cancer. This non-invasive cancer treatment may soon be used with metastasised cancer.
PDT has actually been around for over a hundred years when Oscar Raab noted that an acridine dye killed primitive protozoa when the sun shone. Working with his supervisor von Tappeiner, he determined this was due to oxygen production and in 1905 they cured a lip cancer using the same principal. Unfortunately the methodology was too rudimentary and time consuming.
Until about 2010 the chemical agent was usually photofrin, but now algae, bacteria and even fireflies are being studied. The lights used as energy sources in the work of Raab have been replaced by UV, lasers and ultrasound.
PDT is being studied across the globe from Russia to America, such is the potential of this non-invasive treatment if it can be made to work. It could potentially be used in one treatment to kill every cancer cell in your body.
What is Photodynamic Therapy?
Basically a substance is injected into the body and finds its way into the cancerous cells wherever they are. Then light of a particular frequency was shone onto the location of the cancer and the original injected substance becomes active and kills the cell.
The Dove Clinic’s website had this to say: Photodynamic therapy takes advantage of a chemical interaction between light and a light-activated drug (photosensitizer) to start a series of chemical reactions that kill tumors. Certain physiological properties of tumor tissue cause the photosensitizer to be retained in tumors, but excreted from most healthy tissue. When laser light of a certain wavelength is shined on the tumor, the drug contained within it is converted to an active form that creates toxic molecules, killing cancer cells. Although the drug and light together are powerful, neither has any tumor-killing effect alone. Tumors usually shrink within one to two days of therapy. However, the laser light can only penetrate about one centimeter, or one-quarter inch, into tissue, so large bulky tumors often require repeated light exposure.
Interest takes several strategies. One follows the work of Otto Warburg who won his Nobel Prize for showing oxygen was the enemy of a cancer cell. Over the last 20 years some studies have looked into agents that could lock onto a cancer cell and be energised to release oxygen, which would kill the cancer cell but leave the surrounding tissues unharmed.
Why has PDT suddenly become of interest?
The reason for the new levels of interest is that historically, PDT was limited by the ’photosensitive agent’ and the light form. Most usually, the cancer had to be on the surface or close to the surface of the body. The light could then be shone on the skin.
The agent itself was often limited and a chemical compound or drug - it didn’t lock onto every cancer cell, and/or it locked onto some healthy ones as well. Side-effects were actually common and these often meant not going out into the sunlight.
Two developments have been significant.
* Firstly, there has been a great improvement in the efficacy of the agent, and a focus on the production of ’singlet oxygen’. Natural compounds are being used as agents (like algae and chlorophyll compounds). These travel through the body far more easily that old fashioned chemicals, some are far more effective at locking onto cancer cells and pre-cancerous cells throughout the body, and such ’green’ compounds naturally produce oxygen when energised. Thus more of the rogue cells are killed and there is no harm to the healthy cells.
* Secondly, there has been a surge in the development of potential energy forms. No longer is the treatment limited to superficial cancers on or near the skin surface. Light of very specific frequency, lasers and even energy forms like ultrasound mean that no cancer cell is safe anywhere in the body!
The combination of these two developments has produced a real step-change in PDT.
For example, Cancer Research UK, working with the Gray Cancer Institute in Middlesex, found that a colourful combination of red light, blue dye and a plant hormone can be used to kill cancer cells. Their study reported in the journal ’Cancer Research’ shows the treatment could be very effective when using a plant hormone that in nature helps plants grow towards the sun.
PDT is now an officially approved cancer treatment
PDT was approved by the U.S. Food & Drug Administration (FDA) for the treatment of late-stage oesophageal cancer in 1996. Since then, many other cancer approvals have been issued by the FDA - for example, for early and late-stage lung cancer. PDT is considered most useful where local treatment of tumors is desired, such as in eliminating early cancer or shrinking large tumors that block important structures, like the oesophagus or airways.
It is also approved for medical treatments beyond cancer, for example, actinic keratoses, precursors of skin cancer, and age-related macular degeneration, the leading cause of blindness in the elderly.
In the UK, PDT is slowly moving into the mainstream of cancer treatment. UK cancer Tzar Professor Mike Richards commissioned a Department of Health Report. PDT is likely to be made more available and funded on the NHS. Interest is growing particularly for treatment of prostate, pancreatic and brain tumours.
Work on PDT in humans began in the 1970’s. Literally thousands of people were treated in clinical trials before PDT was approved by the FDA. The early scientists in this field often paid for their research out of their own pockets because grants for PDT were nearly non-existent.
Scientists at the Institute treated cancer cells with a special blue dye that becomes chemically energised in response to light. They also treated these cells with a plant hormone. When they shone red light on to the cancer cells the hormone shattered to produce toxic chemicals called free radicals, which form poisonous by-products with the potential to kill cancer cells.
Sir Paul Nurse, Chief Executive of Cancer Research UK, says: "This is fascinating work in that it combines using clever technology with something provided by nature - plant chemicals. It is a further step in the direction of producing a therapy that directly targets a cancer tumour."
One new PDT drug, developed by Ray Bonnett at the Royal London Hospital is Foscan - basically a very powerful chlorine. This is used with a small diode laser. "You can now get a diode laser to produce any wavelength of light and you can match the wavelength to the absorption frequency of the drug in question. What makes PDT so attractive is the capacity of the surrounding tissue to heal from this treatment, there are no lasting effects and it is repeatable."
The advantages of PDT
PDT has several advantages. There are no cumulative toxic effects, immune or vitamin D damage, or even the possibility of drugs actually causing metastases as there are with orthodox medical treatments for cancer. PDT procedure can therefore be repeated several times if needed. It is non-invasive and repeatable. It does not leave the patient battle weary.
PDT works on virtually all types of cancer. It is not specific to the cell type of the cancer, like chemotherapy agents or radiation.
PDT is usually an outpatient procedure, so the person can go home the same day. It doesn’t require general anesthesia like surgery. Even people who are too elderly or sick for surgery can have PDT because of its lower risk profile.
The future of PDT - is it here already?
There are so many studies going on currently.
In glioblastomas - the most lethal of brain tumours - some drugs used in PDT, glow when you shine blue light on them", according to Mr Colin Hopper, Consultant neck and head surgeon at University College, London. One drug Gliolan or ALA makes the cancer cells grow pink. Although the cancer may appear localised, it has often spread throughout the brain. Doctors can now get laser light fibres under the skull into the deeper tissue so the light can be delivered almost anywhere.
Professor Mark Emberton in London has been using bacteria from the deep sea-bed which become highly activated when light is around. He has conducted a successful clinical trial using lasers with bacteria for prostate cancer.
Then associate Professor, Mathew Gdovin of the University of Texas in San Antonio has actually patented his PDT treatment - he uses nitrobenzaldehyde as the ’agent’ (which diffuses through a tumour and all associated cells), then he sensitises this with UV light. In research on his PDT treatment with Triple Negative Breast Cancer (TNBC) show a staggering 95 per cent of cancer cells dying within 2 hours. Gdovin is looking at using an agent with cells all over the body. He believes he will be able to stop and even defeat metastatic cancer in just a few years time.
Meanwhile Hopper describes two future developments:
One is with chemotherapy. Some chemo agents don’t work because the cancer cells wrap the chemo agent up into a little package and excrete it. PDT could burst this package. So far (2011) 14 patients have been treated in a phase I Clinical Trial. Proof of Concept now exists for head and neck tumours though not yet with gliomas.
Four or five years away is the Firefly Project. Fireflies make an enzyme called luciferase which breaks a chemical compound called luciferin to produce light. Get the luciferin into cancer cells, and the luciferase will cause light emission and kill them.
That’s the work in hospitals - but PDT doesn’t stop there. For example, Dr. Julian Kenyon at the Dove Clinic in the UK has been working with an algae/chlorophyll agent and ultrasound. It’s called Sonodynamic PDT. No Clinical Trials exist but they do have an impressive record of patient case histories.
Hundreds of PDT research studies
Solid case Histories, some early Clinical Studies, yes. The Mayo Clinic in America lists over 100 research studies on PubMed for the use of PDT in all manner of illnesses from macular degeneration to Barrett’s oesophagus, and from skin problems to cancer.
But not much agreement across the world on the best agent or the best energy system. For the moment we are still a little bit short of the polished article. But already there clearly are examples of increased survival. And the potential is huge.
I leave the last comments to the website of the American Cancer Society. Unfortunately, they seem to confine their comments to PDT that uses Porfrin (also spelled porphyrin):
"Studies have shown that PDT can work as well as surgery or radiation therapy in treating certain kinds of cancers and pre-cancers. It has some advantages, such as:
- It has no long-term side effects when used properly.
- It is less invasive than surgery
- It usually takes only a short time and is most often done as an outpatient.
- It can be targeted very precisely.
- Unlike radiation, PDT can be repeated many times at the same site if needed.
- There is little or no scarring after the site heals.
- It often costs less than other cancer treatments.
PDT cannot be used in people who have certain blood diseases, such as acute intermittent porphyria or people who are allergic to porphyrins. This kind of allergy is rare, but may happen in those who have gotten porphyrins in the past".
Fortunately, the days of porphyrins seem numbered, and the energy technology and natural agent work is going full-stem ahead. The future is really not far away.
Other articles on PDT
Readers might also look at:
1. Sonodynamic PDT
2. A summary of work on PDT
3. A feature from icon magazine - Doing the light fantastic