Researchers have found a candidate drug and biomarker that could be used to treat uveal melanoma, a rare eye cancer.
Uveal melanoma (UM) is a rare eye cancer that begins in pigment-producing cells called melanocytes. These are the cells that give eyes their colour and are found in the back of the eye.
Uveal melanoma is associated with risk factors such as fair complexion, pale eyes, and a higher risk of sunburn. Ireland has one of the world’s highest rates of this rare eye cancer.
Treatment for uveal melanoma is often ineffective
Treatment options for uveal melanoma patients include the complete removal of the eye and radiotherapy directly on the eye. Even after these treatments, the tumour will usually spread to the liver, in one out of two patients. These forms of treatment are life-altering surgery, and many patients will be anxious about their risk of metastatic disease.
Once the cancer has spread to the liver, the treatment options are limited. Only 8% of patients survive beyond two years after metastasis. New ways of identifying or predicting patients whose cancer has spread are needed, as well as new treatments for metastatic uveal melanoma.
This research initially centred around cysteinyl leukotriene (CysLT) receptors as scientists investigated their potential as biomarkers or drug treatments. CysLT receptors are involved in inflammation and are known to contribute to allergic diseases such as asthma. Recently, they have been used in a wide range of diseases including central nervous system diseases and cancer.
Identify new drug options
Researchers from University College Dublin examined patient samples and experimental models to see if levels of these molecules, CysLT receptors were associated with patient survival. They also assessed the efficacy of the candidate drug, 1,4-dihydroxy quininib.
“This research builds on our previous work evaluating compounds that can interfere with CysLT receptors in uveal melanoma cells in the laboratory. We developed a laboratory model of primary uveal melanoma from patient samples and a preclinical model of metastatic uveal melanoma. Then, we used biochemical and pharmacological tests to gather a range of data,” said Dr Kayleigh Slater, postdoctoral fellow and first author of this study.
The preclinical data showed that higher CysLT receptor levels in primary uveal melanoma tumours indicated a poor prognosis. The candidate drug was found to affect the molecular hallmarks of the disease that enable cancer to develop and spread in uveal melanoma models. The researchers also identified a biomarker that appeared to predict which patients will not develop metastatic disease.
“These are positive findings using an Irish cohort of patient samples in a disease that is the primary cause of eye cancer in Ireland. We have shown that this candidate drug can act on the tumour and that the biomarkers could be valuable prognostic tools for clinicians to assess which patients are unlikely to develop metastatic disease. We are immensely grateful to the clinical team in the Royal Eye and Ear Hospital Dublin and the patients who agreed to partake in this study at a very difficult time in their lives,” said Professor Breandán Kennedy.
