Uveal melanoma: laboratory advances and new frontiers in patient care

Abstract

Purpose of reviewTo review recent advancements in the genetic understanding, diagnosis, prognosis, and treatment of uveal melanoma (UM). Recent findingsUM is a molecularly distinct melanocytic malignancy driven by mutations in GNAQ or GNA11, with mitogen-activated protein kinase pathway upregulation. Earlier diagnosis and treatment are important factors for improving life prognosis. These goals can be aided by more objective multimodal imaging risk factors for the prediction of malignant nevus transformation and novel treatment strategies such as customized radiation fields and nanoparticle therapy to reduce vision-threatening treatment side effects. The risk for metastatic disease can be reliably predicted through gene expression profiling or the Cancer Genome Atlas project classification, and combined use of clinical tumor features with molecular data allows for highly individualized patient prognosis. Patients with high-risk UM should be considered for clinical trials of adjuvant therapy to prevent metastatic disease. For patients with clinically evident metastasis, combination immunotherapy regimens, T cell-based therapies, and focal adhesion kinase inhibitors offer hope for improved clinical response rates.

The construction of a hypoxia-based signature identified CA12 as a risk gene affecting uveal melanoma cell malignant phenotypes and immune checkpoint expression

“…Molecular pathogenesis and targeted therapy have been novel research topics and promising strategies to prevent UM processes or improve patient survival ( 2 ). Currently, many molecular features have been applied to indicate the patient prognostic diversity, such as that active mutation of the Gα11/Q pathway drives the tumorigenesis of UM and BAP1, SF3B1 , and EIF1AX mutant precited metastatic progression ( 3 ).…”