Mayo Clinic researchers have developed organoid models to study uveal melanoma, one of the most common types of eye cancer in adults. Their goal is to use these models to better understand how this disease works and to develop treatments for unfulfilled patient needs.
Organoids are 3D models grown from patient tissue that accurately reflect the unique genetic and biological characteristics of a patient, also known as ‘avatars’. When derived from a patient’s cancer tumor, an organoid will behave and respond to treatments outside the body in a laboratory (in vitro), just as the original tumor in the body (in VIVO) would be.
In 50% of patients, uveal melanoma metastases, spreads to other parts of the body, which leads to a poor prognosis and average survival of less than two years. Unfortunately, the current treatments for this condition often have limited effectiveness, so that patients and their doctors have few options.
The hope is that the patient derived from the patient is better represented in the Laboratory. The use of these models as the basis for testing medicines will facilitate new treatment discoveries with higher success rates in clinical studies, which is ultimately translated into improved results for patients with uveal melanoma. ”
Lauren Dalvin, MD, an ocular oncologist and surgeon scientist from Mayo Clinic, one of the main researchers
In the past, the lack of models for human diseases that represent the entire uveal melanoma spectrum has created a bottleneck, limiting the ability of scientists to identify effective goals for treatment and prevention. Most laboratory studies come from the same series on the market available cell lines, which are not representative of the disease and often differ from the original tumors in important ways.
To explode this bottleneck, a study team led by Dr. Dalvin, in collaboration with Martin Fernandez-Zapico, MD, a cancer biologist at Mayo Clinic Comprehensive Cancer Center, a new, uveal melanoma-patient-defined organoid biobank. Their goal is to create a research source that represents the Real-World variability of this cancer.
In a paper published in Investigative Ophthalmology & Visual Science, they described the first development of this Biobank. The researchers successfully created organoids derived from Mayo Clinic Ocular Oncology Patients who registered for a prospective study in which tumor tissue was submitted for research from 1 July 2019 to 1 July 2024. Their study determined that these organoid models:
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Retained the clinically relevant characteristics of the original tumors, clustered in suitable molecular groups based on validated prognostic markers and resembled human diseases compared to in VIVO animal models.
The researchers acknowledge the immense value of this organoid -biobank and have already started expanding other research centers. Their goal is to create a source that is able to display the global epigenomic variability of uveal melanoma. In the future they hope that this biobank will serve as an extensive platform for the screening of drugs and other types of laboratory research into uveal melanoma. This cooperation effort will accelerate research and release the road for improved treatments and results for patients with this disease.
Organoids transform the landscape of biomedical research. Scientists use this innovative approach to model diseases, follow their progression and identify and characterize potential treatments. Mayo Clinic is at the forefront of organoid research and applies this approach to study a wide range of health problems, including:
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Neurodegenerative and neurological disorders, such as Lewy Body Dementia, Alzheimer’s disease, autism, opioid addiction and alcohol use disorder.
The goals of this research extend much further than its current applications. Mayo Clinic researchers want to develop organoids that represent organs throughout the human body to follow diseases, screen medicines and regenerate tissues. This approach means the promise to accelerate research in precision medicine and the search for treatments in other areas of biomedical research.
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Journal Reference:
Dalvin, La, et Alt Alto. (2024). New uveal melanoma from patient-derived organoid models recapitulate human diseases to support translational research. Research Halmology and Visual Science. doi.org/10.1167/iovs.65.13.60.