Neoadjuvant Chemotherapy with or Without Talniflumate for the Treatment of Breast Cancer

Summary

RATIONALE: Talniflumate, a prodrug of niflumic acid with significant anti-inflammatory properties, has emerged as a promising candidate in breast cancer therapy due to its ability to modulate key oncogenic pathways. Its mechanisms of action include the inhibition of cyclooxygenase (COX) enzymes, which mitigates tumor-promoting inflammation and fosters a less permissive microenvironment for cancer progression. Additionally, talniflumate disrupts ionic homeostasis by targeting calcium-activated chloride channels (CaCCs), leading to impaired cellular proliferation and potential induction of apoptosis. The agent also exhibits anti-angiogenic activity by downregulating vascular endothelial growth factor (VEGF), thereby restricting tumor vascularization and growth. Furthermore, talniflumate shows potential as a chemosensitizer, enhancing the cytotoxic effects of standard chemotherapy and improving therapeutic outcomes while reducing chemoresistance. These multifaceted mechanisms highlight the therapeutic promise of talniflumate in breast cancer, warranting further preclinical and clinical studies to validate its efficacy, refine dosing strategies, and define its role in combination therapies. PURPOSE: To assess the therapeutic efficacy of Talniflumate in the management of breast cancer, with a focus on its synergistic interactions with neoadjuvant chemotherapy.

Timeline

Start

2025-06-01

Primary completion

2030-12-01

Completion

2030-12-01

Publications

• Background Wang X, Chen B, Zhang H, Peng L, Liu X, Zhang Q, Wang X, Peng S, Wang K, Liao L. Integrative analysis identifies molecular features of fibroblast and the significance of fibrosis on neoadjuvant chemotherapy response in breast cancer. Int J Surg. 2024 Jul 1;110(7):4083-4095. doi: 10.1097/JS9.0000000000001360.
• Background Spanheimer PM, Reeder-Hayes KE. Breast surgery after neoadjuvant chemotherapy: time for a change? Lancet Oncol. 2022 Dec;23(12):1477-1479. doi: 10.1016/S1470-2045(22)00649-0. Epub 2022 Oct 25. No abstract available.
• Background Rao CV, Janakiram NB, Madka V, Kumar G, Scott EJ, Pathuri G, Bryant T, Kutche H, Zhang Y, Biddick L, Gali H, Zhao YD, Lightfoot S, Mohammed A. Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer. Cancer Res. 2016 Apr 1;76(7):1965-74. doi: 10.1158/0008-5472.CAN-15-2820. Epub 2016 Feb 15.
• Background Agostini A, Guerriero I, Piro G, Quero G, Roberto L, Esposito A, Caggiano A, Priori L, Scaglione G, De Sanctis F, Sistigu A, Musella M, Larghi A, Rizzatti G, Lucchetti D, Alfieri S, Sgambato A, Bria E, Bizzozero L, Arena S, Ugel S, Corbo V, Tortora G, Carbone C. Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer. J Transl Med. 2023 Nov 23;21(1):843. doi: 10.1186/s12967-023-04733-z.

Drugs

Indications