J Cancer 2021; 12(15):4672-4685. doi:10.7150/jca.53954

Review

Hindsight: Review of Preclinical Disease Models for the Development of New Treatments for Uveal Melanoma

Caoimhe Goldrick1, Letizia Palanga1, Bobby Tang2, Grace Mealy1, John Crown1,3, Noel Horgan2, Susan Kennedy1,2, Naomi Walsh1✉

1. National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin, Ireland.
2. Royal Victoria Eye and Ear Research Foundation, Royal Victoria Eye and Ear Hospital, Adelaide Road, Dublin, Ireland.
3. Department of Medical Oncology, St. Vincent's University Hospital, Dublin, Ireland.

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Citation:
Goldrick C, Palanga L, Tang B, Mealy G, Crown J, Horgan N, Kennedy S, Walsh N. Hindsight: Review of Preclinical Disease Models for the Development of New Treatments for Uveal Melanoma. J Cancer 2021; 12(15):4672-4685. doi:10.7150/jca.53954. Available from https://www.jcancer.org/v12p4672.htm

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Abstract

The molecular, histopathological, genomic and transcriptomic characteristics of uveal melanoma (UM) have identified four molecular subgroups with different clinical outcomes. Despite the improvements in UM classification and biological pathology, current treatments do not reduce the occurrence of metastasis. The development of effective adjuvant and metastatic therapies for UM has been slow and extremely limited. Preclinical models that closely resemble the molecular and genetic UM subgroups are essential for translating molecular findings into improved clinical treatment. In this review, we provide a retrospective view of the existing preclinical models used to study UM, and give an overview of their strengths and limitations. We review targeted therapy clinical trial data to evaluate the gap in the translation of preclinical findings to human studies. Reflecting on the current high attrition rates of clinical trials for UM, preclinical models that effectively recapitulate the human in vivo situation and/or accurately reflect the subtype classifications would enhance the translational impact of experimental data and have crucial implications for the advancement of personalised medicine.

Keywords: uveal melanoma, preclinical disease models, personalised medicine, cell lines, PDX, GEMM, zebrafish models