This project seeks to identify cellular pathways that could be targeted to treat or prevent cancer in FA. The investigators take a novel approach using a high-resolution CRISPR knockout library to screen for fitness genes and FANCA-specific cancer vulnerabilities. They will take advantage of their one-of-a-kind cell lines derived from primary human tumor specimens taken from FA patients. They will also screen for genes that affect oxygen-tolerance, hoping to identify candidate targets for chemoprevention in FANCA-mutant cells. The investigators propose that this state-of-the-art approach will reveal oncogenic drivers specific for tumor cells and that this information can be further exploited to identify drug targets for FA-associated tumors.
The aim of this grant was to address the challenge of FA head and neck cancer. The team of researchers from Amsterdam used whole exome and whole genome sequencing of DNA in FA cancer cell lines to show that specific changes that happen in FA cancer can be targeted therapeutically. The results demonstrated that the amplification of chromosome 11q22.2, which is associated with the overexpression of the BIRC2-3 gene, is common in FA head and neck cancers. The research team is now working to determine whether chemotherapy approaches targeting BIRC2-3 can be used as a treatment for FA head and neck cancers.
As of 2022, the Amsterdam team is in the process of applying for additional grant funding to continue the study.
Researchers: Josephine Dorsman