Effective drug treatment for a rare type of eye cancer known as uveal melanoma (UM) may soon be on the horizon, thanks to a breakthrough made by a team of international researchers.
Led by experts from University College Dublin (UCD), the groundbreaking study illuminated that the drug ACY-1215, which is also being currently tested for treating other cancers and tumours, is potentially a potent treatment option for combatting advanced uveal melanoma.
This exceedingly uncommon form of eye cancer primarily occurs in Caucasian people and is a particularly fatal form of the disease that currently has limited treatment options. In an effort to overcome these limitations, the research team, which also included investigators from Spain and Sweden, have been analysing a range of pharmaceutical candidates, which led them to ACY-1215.
Dr Husvinee Sundaramurthi, a postdoctoral researcher in the UCD School of Biomolecular & Biomedical Science and UCD Conway Institute, said: “Our research study focused on the drug ACY-1215, which is currently in clinical trials for other solid tumours and blood cancers. We wanted to understand how ACY-1215 works to prevent tumour cell growth and spread in the context of uveal melanoma.”
Uveal melanoma treatment limitations
Uveal melanoma is the most frequent form of eye cancer among the adult population. The cause of the condition is unknown, although we know it is not associated with sun exposure. However, research suggests that fair-skinned people with blue or green eyes are more likely to develop this type of cancer, with the average age of its incidence being between 55 and 60 years. Ireland has one of the highest rates of uveal melanoma, with around 60 people diagnosed annually.
The disease starts to develop in the iris, ciliary body or choroid, which is known collectively as the uvea and is located in the middle layer of the eye. Traditionally, it is treated by targeting cancer cells with ocular radiation implants or through the surgical removal of the eye (Enucleation), meaning a non-invasive drug option could revolutionise therapy.
ACY-1215 is part of a relatively new type of anticancer drug called histone deacetylase inhibitors (HDACi), which perform by impacting proteins known as histones, although the mechanism in which they achieve this is not entirely understood.
Histones tightly package DNA in cells, acting as a spool that the thread of DNA wraps around, with lots of tiny molecules involved in this process. The scientists employed ACY-1215 to interfere with the processes involved in the survival of UM cells, blocking the progression of the disease in laboratory tests and zebrafish.
Breandan Kennedy, Professor of Pharmacology in the UCD School of Biomolecular & Biomedical Science and UCD Conway Institute. Concluded: “We uncovered the particular molecules that may be involved in the anticancer effects the drug ACY-1215 has in advanced UM cells. This study will pave the way to look more closely at the benefits of using HDACi, specifically ACY-1215, as a suitable treatment option for advanced UM. By understanding the full therapeutic potential of these small molecules, we hope to shape advanced UM patient care and personalised treatment strategies for patients.”