Eye cancer: unique insights into oncogenesis: the Cogan Lecture.

The major objective of this lecture is to illustrate how eye cancer research has dramatically affected not only patients with these ocular tumors, but also our fundamental understanding of cancer biology and many other aspects of biomedical research. Retinoblastoma and uveal melanoma, the two most common eye cancers in children and adults, respectively, are very different clinically and biologically. Retinoblastoma is a rare childhood eye cancer that usually occurs before 5 years of age, is often hereditary and bilateral, is caused by the mutation of a single rate-limiting gene, and is rarely fatal if treatment of the eye cancer is successful. Uveal melanoma occurs mostly in older adults, is rarely hereditary or bilateral, is caused by an accumulation of multiple genetic lesions with no single disease-causing gene mutation, and is fatal in up to 50% of patients, even when the eye cancer is successfully treated. Despite these profound differences, retinoblastoma and uveal melanoma have provided unique and complementary insights into the cell cycle, differentiation, development, neoplasia, and other fundamental biological processes. Herein, we will consider some of the highlights in ocular oncology research over the past two decades, starting with the identification of the retinoblastoma gene in 1986. We will examine how the molecular genetics of retinoblastoma has fundamentally altered our view of development, cell cycle and cancer biology. We will then explore the role of the retinoblastoma tumor suppressor pathway in uveal melanoma. Finally, we will review recent exciting research in uveal melanoma that may lead to a significant change in our understanding of that cancer, and we will consider the far-reaching implications of this breakthrough in future research, clinical trials, and patient care.