Synthetic Lethality Related Tumor Models

Synthetic lethality, where combining two non-lethal mutations results in cell death, is exploited in cancer therapy, with PARP inhibitors like olaparib targeting BRCA-deficient cells by exploiting this interaction.  Werner syndrome helicase (WRN) is a synthetic lethal target in cancers with microsatellite instability due to impaired DNA mismatch repair.  WRN is synthetically lethal with MLH1, a protein involved in mismatch repair.

In another example of synthetic lethality, homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a targetable vulnerability. When the MTAP gene is deleted, methylthioadenosine accumulates and selectively inhibits PRMT5. This creates a synthetic lethal dependence on PRMT5 in MTAP-deleted tumors.

To support the discovery and optimization of new PRMT5 inhibitors, WuXi AppTec has established an extensive panel of PRMT5 related CDX/PDX models.  We also offer a broad panel of CDX/PDX models based on BRCA deficiency and WRN related synthetic lethality approaches.

Synthetic Lethality Related Tumor Models

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