Oncology
Turning metabolic vulnerability into an opportunity for cancer treatment
CV6-168 is a potential first-in-class oral, selective dUTPase inhibitor designed to harness metabolic synthetic lethality and induce the Genomic Uracil Stress Response when combined with thymidylate synthase inhibitors such as 5-FU, capecitabine and pemetrexed.
CV6-168 is being evaluated in an ongoing Phase 1a clinical trial in Northern Ireland and Great Britain.
TS inhibitors work by depleting thymine, one of DNA’s four building blocks (A, T, C and G). Without thymine, cancer cells cannot copy their DNA properly. But many cancers find ways around the blockade or evolve resistance over time, limiting what these cornerstone therapies can do.
CV6-168
Thymidylate synthase inhibitors limit the supply of thymidine cancer cells need to make DNA. CV6-168 inhibits dUTPase, a metabolic safeguard that limits uracil incorporation into DNA. Together, these interventions are designed to increase DNA uracilation and push cancer cells beyond their capacity to maintain DNA integrity.
The resulting genomic uracil stress engages the Genomic Uracil Stress Response (GUSR), the cellular response CV6 is designed to exploit. In preclinical studies, this approach drives replication stress, DNA damage and cancer cell death, and has also shown immune-associated responses. These findings support investigation of CV6-168 with immune checkpoint inhibitors, including in cancers that respond poorly to immunotherapy.
Learn more about the Phase 1a clinical trial in the ISRCTN registry.
