Therapeutic target for reversing PARP inhibitor resistance in breast cancer

This technology outlines an approach to treat poly-ADP ribose polymerase inhibitor (PARPi) resistant tumors by targeting the FLT1/VEGFR1 signaling pathway.

Unmet Need: Method for overcoming PARP inhibitor resistance in breast cancer

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.

The Technology: Targeting FTL1 to reverse PARP inhibitor resistance in breast cancer

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.

Applications:

• Treatment for BRCA-mutant breast, ovarian, pancreatic, or prostate cancer.
• Method to overcome PARPi resistance
• Diagnostic/research tool for the detection of PARP inhibitor resistance
• Research model for studying PARP activity and function in DNA repair and signaling pathways
• Therapeutic target for drug resistance in breast and other cancers
• Research platform to study FTL1/VEGFR1 pathway in breast cancer and other cancers

Advantages:

• Increases efficacy of approved PARPis that face resistance
• Therapeutic approach for hard-to-treat BRCA-mutant tumors
• Can be used in combination with other therapies
• Reduces cancer recurrence in patients with PARPi resistance

Lead Inventor:

Swarnali Acharyya, Ph.D.

Patent Information:

Patent Pending (WO/2025/064893)

Related Publications:

• Tai Y, Chow A, Han S, Coker C, Ma W, Gu Y, Navarro VE, Kandpal M, Hibshoosh H, Kalinsky K, Manova-Todorova K, Safonov A, Walsh EM, Robson M, Norton L, Baer R, Merghoub T, Biswas AK, Acharyya S. “FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.” EMBO Mol Med. 2024 Aug; 16(8):1957-1980.

Tech Ventures Reference:

• IR CU24001

• Licensing Contact: Kristin Neuman