Oleocanthal functional food products for breast cancer recurrence control

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SUMMARY From Parent Grant (R41CA247025) Triple negative breast cancer (TNBC) represents 20% of the breast cancer (BC) cases in the US. TNBC patients have a poor recurrence-free, overall survival rate, and limited available treatment options. The Mediterranean olive oil-rich diet is documented to reduce BC incidence. (-)-Oleocanthal (OC) is a natural phenolic secoiridoid exclusively occurring in extra-virgin olive oil (EVOO) and it has shown selective anti-BC activities, including preliminary results showing prevention of recurrence of TNBC in animal models. The HGF/Met signaling pathway, a validated major OC molecular target, is likely involved in initiating aggressive and recurrent TNBC in a subset of patients. To improve taste, dissolution and stability, a solid dispersion formulation of OC (OC-X) was recently developed and characterized. We hypothesize that the EVOO powdered formulation of OC, OC-X, could be developed as a nutraceutical product to help control locoregional TNBC recurrence. This will be tested in the following Specific Aims. In the first aim, we will perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in a nude mouse model after primary tumor surgical resection. This aim will assess the efficacy of formulations in preventive, treatment, and after completion of paclitaxel neoadjuvant regimen modes. In the second aim, we will perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in the MMTV-PyMT transgenic mouse model. This immune competent mouse model develops BC mimicking progression seen in human patients and will be used to assess BC recurrence (after surgical excision of early mammary gland tumors) and metastasis following treatment with OC-X. Expected outcomes: EVOO enriched in OC has been safely consumed throughout human history with increasing evidence of effectiveness against many human pathologies, including BC. Given the lack of other safe therapeutic alternatives, OC is a candidate bioactive natural product that could be safe for long-term use to prevent BC recurrence. The data generated by this project will be combined with future studies of OC-X to facilitate commercialization of OC-X as a nutraceutical product to prevent BC recurrence.