Evaluation of the Therapeutic and Adverse Potential Cannabinoids in vision and Uveal Melanoma

Marzia Pendino

Marzia Pendino was awarded an Irish Research Council Enterprise Partnership Scheme (Postgraduate) grant with Breakthrough Cancer Research as the Enterprise Partner

This project investigates the therapeutic potential of cannabinoids in vision and uveal melanoma (UM).  UM is a rare cancer of the eye.  In approximately 50% of cases, liver metastasizes occurs which decreases life expectancy.  Ireland has one of the highest UM incidences worldwide.

During her 4 year PhD, Marzia will analyse the expression of cannabinoid CB1 & CB2 receptors in human UM cell lines and patient/xenograft samples. She will test if cannabinoid drugs modulate cancer hallmarks (proliferation, metabolism, angiogenesis) in human primary/metastatic UM cell lines and zebrafish xenografts. Marzia will also determine if cannabinoids can restore vision in zebrafish models of blindness. This study will potentially lead to new therapies for UM.

RESEARCH FINDINGS

Publications

Tonelotto V, Costa-Garcia M, O’Reilly E, Smith KF, Slater K, Dillon ET, Pendino M, Higgins C, Sist P, Bosch R, Passamonti S, Piulats JM, Villanueva A, Tramer F, Vanella L, Carey M, Kennedy BN. 1,4-dihydroxy quininib activates ferroptosis pathways in metastatic uveal melanoma and reveals a novel prognostic biomarker signature. Cell Death Discov. 2024 Feb 10;10(1):70. doi: 10.1038/s41420-023-01773-8. PMID: 38341410.

Marcone S, Spadavecchia J, Khan M, Vella G, O’Connell F, Pendino M, Menon M, Donohoe C, Narayanasamy R, Reynolds JV, Maher SG, Lynam-Lennon N, Kennedy B, Prina-Mello A, O’Sullivan J. Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles. Cancers (Basel). 2024 Nov 29;16(23):4007. doi: 10.3390/cancers16234007. PMCID: PMC11640662.

Conference presentations

IARC Conference 2022, Cork, Ireland. Title: “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

AVRO Conference 2022, Denver, USA. Title: “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

Irish Melanoma Forum 2022, Dublin, Ireland. Title: “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

International Cannabinoid Research Society Conference 2022, Galway, Ireland. Title: “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

British Pharmacology Society Conference 2022, Liverpool, UK. Title “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

IARC Conference 2023, Athlone, Ireland. Title: “Evaluating Cannabinoid Receptors as a Therapeutic Target for Uveal Melanoma”

EACR-AACR Basic & Translation Research Conference 2024. Title “The metastatic uveal melanoma cell line DMM 2.5 displays selective sensitivity to the synthetic cannabinoid HU-210.”

Irish Melanoma Forum 2024, Dublin, Ireland. Title: “Targeting Uveal Melanoma with a Potent Cannabinoid: Insights from Cells, OPDX and Patient Biopsy”