research team
Leaders of the research team include, (L to R), Dr. Layla Pires, first author of the study; and Drs. Vanderlei Bagnato, Cristina Kurachi, and Brian Wilson, who are co-senior authors. (Photo: UHN Research Communications)

By UHN Research Communications

Researchers at UHN's Princess Margaret Cancer Centre, along with collaborators at Universidade de São Paulo, have found a method to treat a type of cancer called pigmented melanoma using very short pulses of laser light to activate photosensitive compounds – photodynamic therapy (PDT).

"PDT is a cancer treatment that works by using light to kill cancer cells," says Dr. Layla Pires, scientific associate in the Wilson Lab at the Princess Margaret and first author of the study.

"However, it has not been very effective against pigmented melanoma because the pigment in the cancer cells, called melanin, absorbs too much of the light, making it less effective."

Melanoma is the most lethal form of skin cancer. It originates from melanocytes – cells that produce melanin. Although melanoma occurs predominantly in the skin, it is also the most prevalent eye malignancy in adults.

"Although these eye tumours are relatively small, they are very difficult to treat," says Dr. Cristina Kurachi, professor at the Universidade de São Paulo in Brazil and co-senior author of the study. “Current treatments involve radiation therapy or the removal of the eye.

"Additionally, despite high levels of local disease control, 50 per cent of patients develop metastatic disease which leads to an average survival of only 13.4 months from time of metastatic diagnosis."

The research team sought a way to use light therapy for the treatment of eye tumours. They investigated an alternative type of PDT using extremely short pulses of light.

"We used both pigmented (melanin-containing) and non-pigmented melanoma cells, incubated them with the photosensitive compounds (photosensitizers), and then exposed the cells to pulses of laser light about a tenth of a billionth of a second in duration," says Dr. Vanderlei Bagnato, professor at the Universidade de São Paulo, and co-senior author of the study. "Following this, the team performed the same treatments in preclinical models."

Melanin granules in the melanoma cells act as a “go-between" substance to activate cancer cell death. 1) Inside the melanoma cell, melanin granules absorb photons from the pulsed, near-infrared laser beam; 2) Melanin granules transfer energy to the photosensitizers directly or in the form of fluorescent light; 3) Excited photosensitizers react with oxygen and generate reactive oxygen species that attack cancer cell membranes. (Illustration by Mimi Guo, Princess Margaret Cancer Centre)

The ability of the light to kill the melanoma cells and the destruction of tumours was then assessed using various molecular markers of cell death and staining of tumour tissue.

Results showed that tumours were eradicated in these preclinical models. There was also a highly localized effect that prevented damage to surrounding normal eye tissues.

"We found that when very short pulses of light are used, melanin can efficiently absorb two light photons simultaneously within a given laser pulse," says Dr. Brian Wilson, Senior Scientist at the Princess Margaret and co-senior author of the study. "This absorbed energy is then transferred to the photosensitizer molecules to kill the cancer cells.

"Instead of blocking the light, melanin now acts as a 'go-between' molecule that activates the therapeutic reaction," explains Dr. Wilson, who is also a professor of Medical Biophysics at the University of Toronto.

This study is the first to demonstrate the use of light for treating pigmented tumours in the eye. It also uncovers a novel mechanism in which the light energy is first absorbed by the melanin pigment in the tumour cells as an intermediate step toward activating the photosensitizing molecules. 

"We hope this new, minimally invasive treatment will translate into the clinic, and patients with eye tumours will benefit from its potential to eradicate the primary tumour and prevent metastatic spread," says Dr. Pires.

This work was supported by The Princess Margaret Cancer Center Foundation, Universidade de São Paulo, Brazil, the University of Toronto, the Cancer Prevention and Research Institute of Texas, the Governor's University Research Initiative, the National Council of Scientific and Technological Development CNPq, Science Without Borders, Coordination for the Improvement of Higher Level Personnel (CAPES), the Canadian Institutes of Health Research and the Vision Science Research Program.

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