Newswise — Retinoblastoma is a rare pediatric cancer with approximately 250-300 new cases each year in the United States and approximately 8,000 worldwide. This cancer grows in the retina, a thin layer of cells at the back of the eye, and is often treatable if diagnosed early. However, if left undiagnosed, retinoblastoma can metastasize and lead to death. Over the past decade, research has led to significant progress in understanding the disease. David Cobrinik, MD, PhD, contributed to many of these advances through his work at the Vision Center at Children’s Hospital Los Angeles. Recently, Dr. Cobrinik was invited to write an article on the current understanding of the development and progression of retinoblastoma. This article was published in the New England Journal of Medicine.
Retinoblastoma occurs when a specific genetic mutation occurs in a gene called RB1, a tumor suppressor gene. RB1 tells the body to make a protein called pRB. Since the gene’s discovery, when CHLA researchers and others first cloned it for study in the 1980s, research has revealed much about how RB1 and pRB suppress tumorigenesis. “pRB basically inhibits cell growth,” said Dr. Cobrinik, principal investigator in the Department of Ophthalmology at the Saban Institute. “However, further studies of the pRB protein showed that it is normally expressed in nearly all cells in the body, so it was a mystery why children carrying the inactive RB1 gene developed tumors primarily in the retina.
The Cobrinik lab discovered that the retinal cells in which retinoblastoma originates are cones, the color-sensing cells in the back of the eye. They then showed that cancer only develops when the cones are at a specific intermediate stage of development, after the cones are immature but before they are fully developed and used for vision. They found that these “mature cones” were extremely sensitive to mutations in the RB1 gene. This is one of the earliest demonstrations that cancer can start at specific stages of cell development.
Their research also showed that these cones form something called a precancerous lesion, which is thought to be a dormant precursor to cancer. From birth to around 5 years of age, this condition may turn into cancer. Additionally, after retinoblastomas form, they acquire additional mutations that make the cancer more aggressive, harder to treat, and more likely to metastasize.
All the new insights into how retinoblastoma develops reveal potential therapeutic targets for treating this cancer in the future. It also coincides with the development of a new biopsy method that allows physicians to determine the stage of retinoblastoma before treatment is initiated, by Jesse L. Berry, MD, and Liya Xu, PhD, of CHLA’s Ocular Oncology Group developing. It is expected that this new understanding of how tumors form, combined with new diagnostic methods, will significantly improve retinoblastoma prognosis, especially for patients whose retinoblastoma is only first detected at an advanced stage.
Dr. Cobrinik was recently recognized by the International Society of Hereditary Eye Disorders and Retinoblastoma for his many contributions to the understanding of this disease. “I felt very lucky and honored to be able to deliver the award speech last summer,” said Dr. Koblinik. “We know a lot about this disease. We can now envision new paradigms for retinoblastoma treatment in the future.
Dr. Cobrinik’s work is funded by NIH R01CA137124, the Neonatal Blindness Research Fund, the AB Reins Foundation, and the Templar Eye Foundation.
About Children’s Hospital Los Angeles
Founded in 1901, Children’s Hospital Los Angeles is at the forefront of pediatric medicine and is the largest provider of children’s hospital care in California. Children’s Hospital is home to renowned experts across disciplines who work together to provide inclusive and compassionate care and drive advancements that set pediatric standards nationally and globally. Children’s Hospital Los Angeles provides the world’s best level of care to a truly diverse population of children. The hospital is consistently ranked in the top 10 nationally on U.S. News & World Report’s Best Children’s Hospitals Honor Roll, ranking No. 1 in California and No. 1 in the U.S. Pacific region. Children’s Hospital Los Angeles’ mission is to create hope and build healthier futures. Children’s Hospital Los Angeles is one of the top 10 children’s hospitals funded by the National Institutes of Health. The Saban Institute at Children’s Hospital Los Angeles supports a full range of research, enabling doctors and scientists to translate discoveries into treatments and bring answers to families faster. The Pediatric Academic Medical Center is also one of the largest pediatrician training programs in the United States. CHLA’s commitment to combating food insecurity, enhancing health education and literacy, and introducing more people to health care careers exemplifies the hospital’s commitment to building strong communities. To learn more, follow CHLA Facebook, Instagram, LinkedIn, Youtube and Xformerly known as Twitter, and visit CHLA.org/blog.
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