Therapeutic target for reversing PARP inhibitor resistance in breast cancer

This technology is a targeted therapeutic approach utilizing FLT1/VEGFR1 antagonists to treat poly-ADP ribose polymerase inhibitor (PARPi) resistant tumors.

Unmet Need: Method for overcoming PARP inhibitor resistance in BRCA-mutant tumors

Tumors with cancer cells deficient in homologous recombination-mediated DNA repair, such as BRCA-mutated breast cancers, may be treated with poly-ADP ribose polymerase inhibitors (PARPis). Various PARPis have been shown to be initially effective, but patients later develop resistance, leading to cancer recurrence. The identification of signaling pathways contributing to the development of PARPi resistance can suggest therapeutic vulnerabilities for resistant tumors and permit the use of combination therapies for increased efficacy.

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

This technology identifies a direct mechanistic relationship between the FLT1/VEGRF1 signaling pathway and the development of PARPi resistance in breast cancer cells. PARPi-resistant breast tumors show increased FLT1 expression, which, when targeted with antagonists, resensitizes tumors to PARP inhibition. 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 cancer
• Method to overcome PARPi 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 (US19/550,689)

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