Summary: The Murray laboratory investigates novel therapies and combined modality treatments for retinoblastoma and ocular melanoma. Findings in experimental models are translated directly to Dr. Murray's oncology clinic.

Timothy G. Murray, M.D.
Professor of Ophthalmology
Secondary Appointment in Radiation Oncology

View published research articles by this doctor in the National Library of Medicine.

Current Research Summary: The broad long-term objective of the lab is to improve treatment of children with intraocular retinoblastoma. This form of cancer is the most common intraocular malignancy in children. Retinoblastoma comprises 3% of registered tumors in children under the age of fifteen years and represents one of the most common malignant tumors of childhood with an incidence of 1 in 15,000 live births. Both genders are equally affected with an average age at onset of approximately twelve months. Both eyes are typically involved in the heritable form of the disease and these children are first seen with intraocular tumors at an even earlier age, averaging four months old at presentation.

Retinblastoma tumors derive from malignant transformation of either a primitive neuroectodermal or photoreceptor cell by mutation of the retinoblastoma gene at chromosomal locus 13q14. Systemic mutations at this locus also play a pivotal role in the development of other cancers and predispose children to a lifelong risk of increased cancer development.

Over the last century, significant advances in screening and treatment have led to a cure of the primary tumor for virtually all children. However, this was not without cost, as treatment involved removal of the tumor-containing eye and thus blindness in bilateral cases. Recently, clinical advances have focused on methods for increased tumor control and globe conservation with attendant preservation of sight. These advances have greatly improved the quality of the outcome, but are associated with their own complications.

Our goal is to decrease acute and long-term complications associated with treatment of primary retinoblastoma. Over the last decade, external beam radiotherapy has virtually been eliminated as an initial treatment option in childhood melanoma and has been replaced by systemically delivered chemotherapy coupled to local tumor treatment with laser ablation or cryoablation. Unfortunately, complications during this treatment are expected to occur in up to two-thirds of treated children. The ability to focally deliver chemotherapy (relatively easy due to the unique accessibility and anatomy of the eye and orbit) has been shown to be effective in pilot laboratory studies and in early pilot treatment projects in children with retinoblastoma.

We are using a transgenic model of retinoblastoma and an experimental model of ocular pharacokinetics to evaluate, for the first time, the efficacy and toxicity of systemic chemotherapy, focal/subconjuctival chemotherapy, external beam radiotherapy, and hyperthermia by determining intraocular pharmacokinetics, electroretinography, ocular histology, and in vivo tumor control. These individual therapies will then be combined in order to determine the most efficacious and least toxic treatment strategies for control of advanced retinoblastoma. Our recent pilot data has suggested a differential mechanism of tumor control for chemotherapy and radiotherapy in retinoblastoma that will be evaluated as a target for future therapies. As we obtain results from our work, we translate our findings immediately to the clinic for the care of children with this devastating ocular malignancy.