Researchers at UHN’s Princess Margaret Cancer Centre (PM) 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. 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,” says Dr. Layla Pires, first author of the study and Scientific Associate in the Wilson Lab at PM.
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. Current treatments involve radiation therapy or the removal of the eye,” says Dr. Cristina Kurachi, Professor at the University of São Paulo, Brazil, and co-senior author of the study. “Additionally, despite high levels of local disease control, 50% 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. Following this, the team performed the same treatments in preclinical models,” says Dr. Vanderlei Bagnato, Professor at the University of São Paulo, Brazil, and co-senior author of the study. 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 PM 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,” Dr. Wilson explains.
This study is the first to demonstrate the use 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.
(L-R): Dr. Layla Pires, first author of the study; Drs. Vanderlei Bagnato, Cristina Kurachi, and Brian Wilson, co-senior authors of the study.
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.
Dr. Brian Wilson is a Professor of Medical Biophysics at the University of Toronto.
Pires L, Khattak S, Pratavieira S, Calcada C, Romano R, Yucel Y, Bagnato VS, Kurachi C, Wilson BC. Femtosecond pulsed laser photodynamic therapy activates melanin and eradicates malignant melanoma. Proc Natl Acad Sci U S A. 2024 Apr 2;121(14):e2316303121. doi: 10.1073/pnas.2316303121. Epub 2024 Mar 29.