Anti-Platelet-Derived Growth Factor Receptor-Beta Therapy Does
Not Trigger Retinal Endothelial Cell Toxicity
Approximately 300 children are diagnosed each year in the
United States with retinoblastoma (Rb), the most common
intraocular cancer among childhood malignancies.
The severity of the disease depends primarily on the size and location of the
primary tumor. If dissemination occurs Rb can spread throughout
the retinal to the vitreous region, central regions of the brain, to
the bones and bone marrow.
Metastases significantly reduce the survival rate. Treatments can include enucleation, systemic or local chemotherapy, focal therapy, radiation therapy and in rare instances stem cell transplantation.
These treatments emphasize on the child’s life first, while vision and preservation of the eye are of
Disruption of the blood-retinal barrier (BRB), leaky vessels and high-levels
of angiogenic responses including vascular
endothelial growth factor (VEGF) and the active platelet-derived
growth factor receptor-beta (PDGFR-β) signaling, are characteristics of Rb.
Therefore, targeting the tumor and the angiogenic
response may provide an alternative therapeutic strategy to this
disease. In the last decade, Rb research has shifted to focus more
on identifying and successfully targeting new pathways that are: 1)
tumoricidal, 2) safer for healthy cells necessary for homeostasis
and, 3) capable of being administered locally. In our pursuit to
develop novel Rb therapeutic strategies we recently identified the
PDGFR-β as being highly active in Rb disease.
We targeted the PDGF-PDGFR-β signaling pathway using imatinib mesylate (IM,
akaGleevec® from Novartis), a protein-tyrosine kinase inhibitor
approved to treat acute lymphoblastic leukemia (ALL) in adults
and children that are Philadelphia chromosome (summarized in)8
positive, among other malignancies, and showed in vitro reduction
of Rb growth, invasion, and survival in an AKT-, MDM2-, and
Ophthalmol Open J. 2020; 4(1): 5-10. doi: 10.17140/OOJ-4-121