Photodynamic Therapy (PDT) and cancer

Photodynamic Therapy (PDT) and cancer
Using non-invasive Photodynamic Therapy (PDT) to kill cancer cells, a short overview by Chris Woollams

Another new ’alternative’ cancer treatment’ is Photodynamic Therapy, or PDT. In reality, it is far from ’new’ having been around for a hundred years or more. To quote from the 2011 interview with Professor Mike Brada of the Royal Marsden, "The basics of this quest have been to take a chemical agent which releases oxygen when light is shone on it. Oxygen kills cancer cells. Historically, the limitations have been that PDT could only be used on the skin or just below it, but laser and even ultrasound energy forms have changed all that making attacks on cancers in the skull and deep tissues more and more possible.

Then there have been significant developments in the agents. Historically these have tended to be chemical - in effect, drugs. Their ability to lock onto only cancer cells and leave healthy cells unharmed was imperfect. Now new agents are being developed rapidly."

No wonder Professor Mike Richards (the former UK cancer ’Tsar’) commissioned a Department of Health report which is expected to ’recommend that funding for PDT be made available’. Specific areas of interest are prostate, pancreas and brain cancers. It is effectively a non-invasive therapy that can be repeated if necessary’. In 2016 work by Professor Mark Emberton using sea-bed bacteria and lasers was heralded as a breakthrough in prostate cancer. In coming years we will almost certainly see the potential of PDT being realised. 

The Background to PDT 

Photodynamic therapy historically used a chemical ’agent’ to lock onto cancer cells in the more superficial areas of the body. This agent was then stimulated by light energy to produce singlet oxygen, which is known to kill cancer cells without harming the surrounding healthy cells. Well, that was the theory.

While there has long been the desire to find non-invasive therapies with far less side-effects than orthodox treatments such as chemo- and radiotherapy, PDT was inhibited by two factors: The ’agents’ or drugs being used and the quality of the light forms available. And there were side-effects; for example a sensitivity to sunlight for 4-6 weeks.

The current uses of Photodynamic Therapy

In the UK, most cancer websites will tell you that PDT is used with cancerous or pre-cancerous conditions of the skin, or near internal organs. Barrett’s Oesophagus and Bowen’s disease of the skin get mentioned along with light sensitive creams for the skin. But that is really only scratching the surface. PDT has huge potential.

NICE has already approved PDT for use with skin cancer (but not melanoma), cancers of the head and neck, lung cancer and oesophageal cancer.

Photodynamic Therapy agents

Work through the 1980s saw the emergence agents such as Photofrin, or Porfirmer Sodium; it is a mixture of oligomers and is used as a photosensitising agent today in a number of American cancer centres. It has been approved by the FDA in 1995/8 for the treatment of oesophageal cancer and non-small cell lung cancer.

Go To: The Future of PDT

The problem with the earlier drugs was that they do have side-effects - allergic reactions, nausea and so on. They also can lock on to health cells and kill those. Uptake was less than perfect.

Colin Hopper, consultant Head and Neck surgeon at University College London Hospital explains " Some of the earlier drugs were fairly crude, A century ago Oscar Raab noted that using an acridine dye killed bugs when exposed to light. Having determined this was due to oxygen release, he and his supervisor, von Tappeiner, cured a lip tumour in a patient. 

Still a ’drug’, one new development has been that of Foscan (or Foscan-PDT), or Temporfin, by Ray Bonnett at the Royal London Hospital. It is basically a very powerful chlorine. It is effective down to a depth of about 1 cm only, and although the surrounding tissue is damaged, it quickly recovers and heals. It has been used with cancers such as basal-cell carcinomas. 

Go To: A feature on PDT from icon magazine

The explosion in work on PDT has uncovered a wide variety of agents some of which are much, much more effective at oxygen release and targeting cancer cells, with less accidental targeting of healthy ones.

Possibly the most exciting developments are coming in the more ’natural’ areas of agents - the development of new agents, like green algae and chlorophyll compounds allows penetration into deeper levels in the body. Chlorophyll has a structure similar to haemoglobin (the former is 4 molecules around a magnesium centre, the latter 4 molecules around an iron central atom). Thus it can move freely in the blood stream to almost any location.

Such ’green’ agents are being studied by orthodox cancer centres and private clinics alike. They don’t just go deeper; cancer cells are simultaneously targeted throughout the body’ according to Dr Julian Kenyon of the private Dove Clinic.

Gliolan is another ’drug’ being used. This has the added advantage of glowing pink when light is shone on it allowing surgeons to remove all the cancerous tissue whenever possible.

And another natural compound is being developed from fireflies, although this is very early days yet. Fireflies make light via an enzyme called luciferase, which breaks the chemical luciferin in half emitting light. "If you can get the luciferase into cancer cells, the cells break the luciferin and kill themselves" says Hopper. Jane Ng is leading the Firefly Project where work has been completed in cell culture and animal studies are next.

PDT can help Chemotherapy work better
Some PDT agents may also help chemotherapy work better. "Some chemo agents", says Hopper, " don’t work well because the cancer cells wrap them up in little envelopes and excrete them before they even have a chance. So the idea is to burst the little packets using PDT. It’s called Photochemical Internalisation or PTI. 14 patients with head and neck cancers have been treated in a Phase I Clinical Trial and we have proof of concept".

PDT - the Energy Forms

There have been significant developments in Energy technology too with the use of lasers. "We can get a small diode laser to produce any wave length of light. The idea is that the activation wave length is matched to the absoption spectrum of the drug in question. Foscan is selective where you shine the light" says Hopper.

But even that has already been surpassed. The use iof other energy forms like Ultrasound has already been shown to allow the ’energisation’ of the agent throughout the body simultaneously. If the agent and ultrasound can be pefected it means every cancer cell throughout the body is potentially vulnerable. And that is huge. Especially as this is a non-invasive treatment. No wonder Mike Richards wanted efforts cranked up.

New technology is rapidly bringing out the true potential of PDT as an Alternative treatment for cancer. Several major hospitals in America now offer PDT; as do a number of private clinics. In America there are a number of centres all over the country using PDT to treat non-small cell lung cancer, oesophageal cancer and Barrett’s oesophagus. A review of Clinical Evidence concluded that there were three randomised Clinical Trials to support usage, but no practice guidelines. I found ten non-controlled Clinical studies. 

The Royal Free Hospital in London has just begun (October 2013) a clinical trial with PDT and breast cancer.
You will need to carefully understand what the ’agent’ to be used can do, and how it is to be activated. For skin cancer PDT is now clearly an alternative; in the UK there is even Ambulite, a ’light-emitting sticking plaster’ that you can wear over the drug covering the cancer, and go home continuing the treatment while you watch the TV and read the paper!

PDT an alternative, non-invasive cancer treatment in the making?

Chris Woollams, former Oxford University Biochemist and a Founder of CANCERactive summed up the current situation, "Although I can see that great strides are being made, and there is no doubt that the Medical Authorities already see enough in the research to approve the use of PDT in hospitals, I still think we are quite a way from the finished article. And this allows some people (both in Medical Centres and Private Clinics) to jump on the bandwagon and, I fear, excitement leads to overclaim.

Can PDT ’cure’ cancer?
Well it does seem to deliver for skin cancers and the agents and energy systems are getting better by the day so the potential is clearly there but we still do not have the fully finished article and it seems early days on deeper located cancers. There are pages and pages of websites on PDT on Google search and everybody is excited. But, for my money, we are five years off at least.

Is there research on PDT, or even Clinical Trials? To date there seem to be no  full randomised, placebo controlled phase III clinical trials. Many hospitals and clinics now have detailed case studies with real stories of patient survival. But as yet there is no real phase III Gold Standard Clinical Trial of, say, PDT with breast cancer or colon cancer. (I am not trying to decry Photofrin here. I just cannot find a randomised, double blind, placebo controlled study). The latest work on Prostate cancer by Mark Emberton moves in the right direction.

It will come. - One day, there will be really strong (probably all natural) agents activated by energy sources such as High Intensity Ultrasound. And they may well be able to knock out cancer cells all over the body - not just the original tumour but all the secondaries.

As an adjunct to orthodox therapy PDT currently may well offer some interest. Clearly oncologists are hoping that it can deliver in rarer cancers like brain tiumours, pancreatic cancers and so on where, personally, I don’t think orthodox medicine offers much.  I come away from writing this understanding totally why there is all this excitement but just feeling more than a little concerned that we are still quite a way off the definitive treatment. Perhaps that is unfair. But take localised hyperthermia, or Ablation, as an example and we already have a non-invasive treatment with 5 UK and Swedish Clinical Trials behind it. And look how that ’alternative’ treatment is struggling to be accepted!  Why is PDT being ’accepted’ when actually its research base seems far poorer?
Photodynamic Therapy (PDT) and cancer
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