Children’s Hospital Los Angeles Researcher Reviews the Current State of Retinoblastoma Research in the New England Journal of Medicine
April 19 2024 - 9:00AM
Business Wire
Retinoblastoma is a rare pediatric cancer, with approximately
250-300 new cases per year in the United States and 8,000
worldwide. The cancer grows within the retina, a thin layer of
cells at the back of the eye, and is usually treatable when
diagnosed early. However, if undiagnosed, retinoblastoma can
metastasize and lead to death. Research has led to remarkable
advances in the understanding of this disease over the past decade.
David Cobrinik, MD, PhD, has contributed to many of these advances
in his work at the Vision Center at Children’s Hospital Los
Angeles. Recently, Dr. Cobrinik was invited to write an article
about the current understanding of the development of
retinoblastoma. The article appeared yesterday in The New England
Journal of Medicine.
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Children's Hospital Los Angeles has been
at the forefront of retinoblastoma research for decades. Dr. David
Cobrinik was invited to review the current state of retinoblastoma
research in the New England Journal of Medicine. (Photo: Business
Wire)
Retinoblastoma occurs when there is a specific genetic mutation
in a gene called RB1, a tumor-suppressing gene. RB1 tells the body
to make a protein called pRB. Since the gene was identified (it was
first cloned for study in the 1980s by CHLA researchers and
others), research has revealed much about how RB1, and pRB,
suppresses tumorigenesis. “pRB basically puts the brakes on cell
growth,” says Dr. Cobrinik, Principal Investigator in Ophthalmology
at The Saban Research Institute. “However, further study of the pRB
protein showed that it is normally expressed in almost all the
cells of the body, so it was a mystery why children who carry an
inactivated RB1 gene mainly develop tumors in the retina.”
The Cobrinik Lab found that the retinal cell of origin for
retinoblastoma is the cones—the color-sensing cells in the back of
the eye. They then showed that the cancer occurs only 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 “maturing cones” are extremely
sensitive to RB1 gene mutations. This was one of the first
demonstrations that cancers can begin in a specific stage of cell
development.
Their studies also showed that these cone cells form something
called a premalignant lesion, considered a dormant precursor to
cancer. This lesion can then convert into a cancer from the time
the baby is born up until about 5 years of age. Moreover, after the
retinoblastomas form, they acquire additional mutations that make
the cancers more aggressive, harder to treat and more likely to
metastasize.
All of the new understanding about how retinoblastomas develop
has uncovered potential therapeutic targets for possible future
treatment of the cancer. It has also coincided with the development
of a new biopsy method that allows doctors to determine the stage
of retinoblastoma before treatments begin, which was developed by
the CHLA ocular oncology team of Jesse L. Berry, MD, and Liya Xu,
PhD. The expectation is that this new understanding of how tumors
form combined with new diagnostic approaches will significantly
improve retinoblastoma outcomes, especially for patients whose
retinoblastoma tumors are only first detected in advanced
stages.
For his numerous contributions to the understanding of the
disease, Dr. Cobrinik was recently recognized by the International
Society for Genetic Eye Disease and Retinoblastoma. “I felt very
fortunate and honored to give the award lecture last summer,” says
Dr. Cobrinik. “We’ve learned a lot about this disease. And we can
now envision a new paradigm for retinoblastoma treatment in the
future.”
Dr. Cobrinik’s work is funded by NIH grant R01CA137124, the
Neonatal Blindness Research Fund, the A. B. Reins Foundation, and
the Knights 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
hospital care for children in California. Children’s Hospital is
home to renowned experts who work together across disciplines to
deliver inclusive and compassionate care, and drive advances that
set pediatric standards across the nation and around the globe.
Children’s Hospital Los Angeles delivers a level of care that is
among the best in the world for a truly diverse population of
children. The hospital is consistently ranked in the top 10 in the
nation on U.S. News & World Report’s Honor Roll of Best
Children’s Hospitals, including No. 1 in California and No. 1 in
the Pacific U.S. region. Children’s Hospital Los Angeles embraces
the hospital’s mission to create hope and build healthier futures.
Children’s Hospital Los Angeles is among the top 10 children’s
hospitals for National Institutes of Health funding. The Saban
Research Institute of Children's Hospital Los Angeles supports the
full continuum of research, allowing physicians and scientists to
translate discoveries into treatments and bring answers to families
faster. The pediatric academic medical center also is home to one
of the largest training programs for pediatricians in the United
States. And the hospital’s commitment to building strong
communities is evident in CHLA’s efforts to fight food insecurity,
enhance health education and literacy, and introduce more people to
careers in health care. To learn more, follow CHLA on
Facebook, Instagram, LinkedIn, YouTube
and X, formerly known as Twitter, and visit
CHLA.org/blog.
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Lauren Song lasong@chla.usc.edu