Frogs bring new hope for patients with desmoid tumors

Desmoid tumors are soft-tissue neoplasms that are slow-growing but very invasive. Despite a clearly defined genetic etiology (Wnt hyperactivation), no specific molecular targets for these tumors have been identified yet, so that apart from surgery and amputation there are hardly any therapeutic options.

Researchers of the team of CRIG group leader Prof. Kris Vleminckx have now established a new methodology called ‘CRISPR/Cas9 selection–mediated identification of dependencies (CRISPR-SID)’ in a diploid frog Xenopus tropicalis model of desmoid tumours to identify new drug targets. By simultaneously targeting a tumor suppressor gene (apc) and candidate dependency genes, and calculating the deviations between experimentally observed gene editing outcomes and deep-learning–predicted double-strand break repair patterns, CRISPR-SID allows to identify genes under negative selection during tumorigenesis.

Using this technology, the researchers identified EZH2 and SUZ12, both encoding critical components of the polycomb repressive complex 2, as dependency genes for desmoid tumors. Moreover, EZH2 inibition via Tazemetostat induced partial regression of the tumors.

Interestingly, Tazemetostat is already approved and used in the clinic to treat patients with other cancer types. Therefore, the drug might find its way to desmoid cancer patients more quickly, as it has already passed several preclinical and clinical studies.

Discover the original article via this link.

Read a Dutch summary of the article in the UGent Durf Denken online magazine via this link.