This technology outlines an approach to treat poly-ADP ribose polymerase inhibitor (PARPi) resistant tumors by targeting the FLT1/VEGFR1 signaling pathway.
Tumors deficient in homologous recombination-mediated DNA repair, such as BRCA-mutated breast cancers, rely heavily on the single-strand break repair protein poly-ADP ribose polymerase (PARP) for DNA repair and maintenance. Thus, these tumors respond well to treatment using synthetic PARP inhibitors (PARPis). While various FDA-approved PARPis are initially effective, patients tend to develop PARPi resistance, resulting in lethal cancer recurrence. Therefore, the ability to reverse acquired PARPi resistance is necessary to improve patient outcomes and increase the efficacy of PARPi treatment for BRCA-mutated cancers.
This technology identifies a relationship between the FLT1/VEGRF1 signaling pathway and the development of PARPi resistance. PARPi-resistant breast tumors show increased FLT1 expression, resulting in the activation of pro-survival pathways and dampening of the cytotoxic immune response. When targeted with FLT1/VEGFR1 pathway antagonists, these tumors become resensitized to PARPi. This technology highlights a potential therapeutic target for reversing PARPi resistance and can help identify therapeutic vulnerabilities for PARPi-resistant tumors, including BRCA-mutant breast cancers.
This technology has been validated in vivo.
Patent Pending (WO/2025/064893)
IR CU24001
Licensing Contact: Kristin Neuman