University of Turku team builds new model for rare, treatment-resistant melanoma

Researchers at the University of Turku have developed a CRISPR-based laboratory model for BAP1-deficient melanoma, a rare cancer with few effective treatment options once it spreads. The tool could speed testing of new immunotherapy combinations for melanoma and other hard-to-treat cancers.

Why it matters: - BAP1-deficient melanoma is rare, aggressive and resistant to current state-of-the-art immunotherapies. - The disease becomes especially deadly after metastasis, with liver spread occurring in roughly half of patients and median survival measured in months. - A reliable immune-competent model could speed drug development for this melanoma and related cancers that share BAP1 loss.

What happened: - Researchers at the University of Turku in Finland created a new pre-clinical tumour model for BAP1-deficient melanoma. - The team used CRISPR-Cas9 gene editing to delete BAP1 from normal melanocyte cells. - The resulting model behaves like human BAP1-deficient melanoma in an animal with a fully functioning immune system. - The study was published in Communications Biology.

The details: - BAP1-deficient melanoma is the most common intraocular malignancy in adults. - Once the cancer metastasizes, it evades the immune system and remains universally resistant to current immunotherapies. - BAP1 loss makes tumours more aggressive, faster growing and better able to suppress immune cells. - BAP1 loss is described as the most important molecular event in uveal melanoma progression. - BAP1 loss also plays a role in mesothelioma, renal cell carcinoma and other cancers. - Scientists had not been able to study BAP1 loss well in the lab because no suitable immune-competent model existed. - Previous models either lacked a functional immune system or included too many other mutations to isolate BAP1’s role. - Lead researcher Dr. Mona Wang Meng said the new model recapitulates the human tumour immune microenvironment in vivo. - Dr. Meng said the platform can be used to test immunotherapy combinations that may overcome treatment resistance.

Between the lines: - The main bottleneck in this area has been the lack of a model that preserves tumour-immune interactions while keeping the immune system intact. - A model that isolates BAP1 loss makes it easier to connect one genetic change to immune evasion and treatment resistance. - Dr. Carlos R. Figueiredo said the platform could help researchers worldwide design and test new immunotherapy combinations. - The broader implication is that BAP1 loss may represent a shared vulnerability across several hard-to-treat cancers, not just melanoma. - The work sits within MIORG and the InFLAMES Research Flagship at the University of Turku, which focuses on using the immune system to fight cancer.

What's next: - Researchers can now use the model to study how BAP1 loss drives immune evasion. - The platform should support preclinical testing of new combination immunotherapies. - The model may also help extend research into other BAP1-linked cancers that have resisted effective treatment.

The bottom line: - The University of Turku team has built a much-needed research tool that could make rare, treatment-resistant melanomas easier to study and, eventually, easier to treat.