4 Questions about Photodynamic Therapy in Cancer Treatments

Despite scientific advances in diagnosis and treatment, as well as advances in care and prevention, cancer remains the second leading cause of death worldwide (9.6 million in 2018). In addition to the symptoms of the disease, patients suffer from the adverse effects of heavy treatments, which sometimes have lifelong after-effects. In this article, we focus on photodynamic therapy, a treatment that has been developing for cancer over the past 40 years, and which offers numerous benefits for patients.

1. What is Photodynamic Therapy?

Photodynamic Therapy (PDT) is a treatment that originated in the early 1980s and has been growing in popularity recently for various conditions like acne, psoriasis or acute macular degeneration. Initially used in cancer for the treatment of skin cancers (and rapidly extended for cancers of the prostate and the respiratory system), it is based on the combined action of three harmless components when taken separately: oxygen, photosensitive agents and light.

PDT kills cancer cell by apoptosis, by producing reactive oxygen species (ROS). Photosensitive agents are introduced at the site of the tumor, in the form of a cream for skin cancers or intravenously near the tumor for other cancers. These agents, which are absorbed within a few hours by the cancer cells (they preferentially accumulate in cells that multiply rapidly) are then activated by a light source of a specific wavelength, which causes them to react with the oxygen in the cells to form free radicals.

In addition to this direct action on the tumor, phototherapy also has two indirect effects:

– PDT damages the vascular network of the tumor. Studies demonstrated that this effect has an important role on the destruction of the tumor.
– PDT triggers an immune response. Its role on the activation of an immune response, notably through an upregulation of the expression of heat shock proteins, is less clear and continues to be studied.

2. What are the benefits of photodynamic therapy in cancer treatment and what are the current challenges?

Despite being studied for 4 decades, photodynamic therapy is still considered as a promising cancer treatment, notably for its potential to improve patients’ quality of life. This is where its role in anti-tumour strategy is growing, due to its positive effects on healing and quality of life of those treated.

It is important to note that photodynamic therapy is rarely used alone or in first line. PDT is in clinic often considered after chemotherapy or surgery to improve both QoL and survival rates. For example, for patients first treated by chemotherapy, PDT showed improvement of the one-year survival rate. In France a study conducted on early-stage prostate cancer also demonstrated the efficacy of PDT on the elimination of the tumor.

Advantages of photodynamic therapy

One of the major challenges in cancer treatment is to specifically target cancer cells and spare healthy tissue. Today, microsurgery makes it possible to be more precise during interventions and highly specific targeted therapies are multiplying, nevertheless the main treatments are still quite damaging. Photodynamic therapy meets this need because it is very selective and non-invasive.

In addition to preserving healthy tissue, photodynamic therapy has other advantages, especially in terms of quality of life:

– Patients are treated on an outpatient basis and does not require either long treatments or complete hospitalization.
– There are few short-term and long-term side effects. Most of the drugs are well tolerated by patients and no scar remain on the healed site.
– The long-term morbidity is reduced compared to other treatments.
– These treatments are relatively inexpensive and can be repeated many times if necessary, unlike radiotherapy, and doesn’t prevent the patient from receiving other treatments in the future.

Challenges of photodynamic therapy

Phototherapy has a limited use for the moment due to the accessibility of light to the area to be treated. Deep or extensive cancers cannot be treated at the moment. It is also recommended for patients to protect themselves from the sun for some time after the treatment, and some side effects (pain, swelling, blisters…) may be experienced.

3. What photodynamic therapy treatments are currently approved for cancer?

The fist photodynamic therapy approved for cancer was Porfimer Sodium, in 1993 for bladder cancer. Since then, it has been extended to other cancers like esophageal cancer and non-small cell lung cancer and is still studied for continued expansion. A second generation emerged, like Aminolevulinic acid for pre-cancerous skin diseases, and many chlorin based PS like Temoporfin or Talaporfin for various types of cancers (exclusively for skin or luminal organs) have been approved.

PDT is a dynamic research field as there are around 50 on-going clinical trials for cancer registered in clinicaltrials.gov. Most of the players are small highly specialized companies dedicated to photodynamic therapy or to oncology.

4. What are the potential evolutions of PDT in cancer treatment?

The main challenge is to extend this treatment option to all cancers. Since light does not pass through tissue, this involves bringing the light source as close as possible to the tumor to be treated. Different strategies have been elaborated and seem promising.

Nano-scintillator-mediated X-ray induced PDT is one of the most studied possibility. Unlike light, which has shallow penetration into tissue, X-rays penetrate easily and can stimulate the emission of light by these nano-scintillators. Hence, this technique combines two treatments, radiotherapy and photodynamic therapy.

Other researchers are evaluating new compounds excited by infrared lights and that don’t rely on oxygen to kill cells.

Using the example of combinations made for other cancer treatments, researchers are looking to develop new photosensitizers combined with albumin. In one study the combination of organoiridium with albumin was identified as a promising candidate due to its high photostability, long photo-phosphorescence and ability to integrate into cancer cells.

Thanks to the low side effect profile of photodynamic therapy and therefore positive impact on patients’ quality of life, we believe that the market potential for this technology is promising. Indeed, quality of life is getting an increasingly important factor in the considerations of payers and physicians. The possibility of combining photodynamic therapy with other therapies to achieve better results without impacting the quality of life of patients offers engaging development prospects. At Alcimed, we will continue to explore this dynamic field of photodynamic therapy to keep you informed of its evolution!

About the author,

Volker, Great Explorer Oncology in Alcimed’s Healthcare team in Germany