Atlas of the Eye: Understanding uveal melanoma

Stanford Cancer Institute member Prithvi Mruthyunjaya, MD,MHS , MD, the Alan Adler Professor of ophthalmology, professor of radiation oncology (by courtesy), and director of the Ocular Oncology Service, is spearheading groundbreaking research in the treatment of ocular cancers, particularly uveal melanoma—the most common primary eye cancer in adults. 

“Eyes are crucial to a patient’s quality of life. Our goal is to preserve life, save the eye when possible, and optimize vision in vision-threatening conditions,” he explained.

Unfortunately, treatment options for metastasis are improving but are still limited. “Tumors in the eye can be controlled using radiation or surgery, but up to 50% of patients develop metastatic disease, particularly in the liver and lungs.”

Mruthyunjaya has helped develop newer techniques to safely perform small sample biopsies of intraocular tumors, which are only a few millimeters in thickness. This information guides melanoma oncologists at Stanford in developing customized screening programs to identify metastatic disease at earlier time points.    

“These biopsies have led to a fundamental understanding of how the biological spread of cancers works, especially in the eye.” 

Stanford’s contributions to ocular oncology extend beyond treatments. Mruthyunjaya and Stanford colleague Vinit Mahajan, MD, professor of ophthalmology, have pioneered the Stanford Ophthalmic Bio-Repository, a prospective ocular tissue collection database that is studying protein signatures from ocular fluid samples taken during these intraocular biopsies. 

“We developed a new technique to examine eye fluids at the highest resolution they’ve ever been, where we can sample over 5,700 proteins from 50 mL of fluids taken from the front of the eye. Our team has created a new protein atlas of the eye, mapping proteins found in the normal fluids in the eye to the original cells that produced those proteins within the eye and the tumor itself. This may help us confirm genetic signatures of melanoma without invasive tumor biopsies,” said Mruthyunjaya. 

Published in Cell, this research explored a new technique coined Temporal Expression of Multiple Protein Origins (TEMPO). This technique enables researchers to study proteins in the front of the eye and link them to a particular genetic expression. It provides new targets and ways to predict patient-treatment outcomes and explains why previously used treatments for melanomas didn’t work. 

This insight could revolutionize personalized cancer treatment in uveal melanoma by identifying which therapies will most likely be effective, moving toward a precision-medicine approach for ocular cancers at less expense to the patient’s health. 

“This could fundamentally change how we treat ocular melanoma, allowing us to monitor lesions at the molecular level and intervene earlier than ever before,” Mruthyunjaya said. “It’s as precision medicine as we can think of right now.”

While this method requires a surgical procedure for the patient, it may be able to be performed in the clinic setting. Mruthyunjaya is currently utilizing the Stanford-pioneered liquid biopsy, a minimally invasive medical test, technique to mitigate these operations. 

By Kai Zheng

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