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Eye cancer is an uncommon tumour that can affect the outer parts of the eye (like the eyelid) or the inside of the eyeball (intraocular cancer). The most common intraocular cancers in adults are melanoma and lymphoma, whereas the most common in children is retinoblastoma, which starts in cells of the retina.
Bland et al. show that cancer types with heterozygous somatic hotspot mutations in the spliceosome component SF3B1 are vulnerable to PARP inhibition, which causes a defective response to replication stress.
Across multiple cancer types, hotspot mutations in SF3B1 confer selective sensitivity to multiple clinically available PARP inhibitors. This sensitivity is due to reduced levels of CINP specifically in SF3B1-mutant cells, which leads to a loss of the canonical replication stress response after challenge with PARP inhibitors.
Metastatic uveal melanoma continues to have a poor prognosis with distinct pathophysiology from cutaneous melanoma and limited effective treatment options. Targeted therapy with darovasertib towards protein kinase C is well tolerated with signals of early efficacy, warranting further exploration and combination strategies.
