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 treatment options. The Mediterranean olive oil-rich diet is documented to reduce BC incidence. (-)-Oleocanthal (OC) is a natural phenolic exclusively occurring in extra-virgin olive oil (EVOO). It showed selective anti-BC activities. Dysregulated HGF/MET pathway, the validated major OC molecular target, correlates with initiating aggressive and recurrent TNBC profile. A unique OC taste-masked, dissolution enhancing and chemical integrity maintaining solid dispersion formulation (OC-X) was developed and characterized. The central hypothesis is that oral OC-X will be effective as a preventive and therapeutic to control locoregional TNBC recurrence. The following aims will test this hypothesis.
Aim 1 : Perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in nude mice and pharmacokinetics in Swiss albino mice.
This Aim will assess efficacy of OC-X in preventive, treatment, after completion of paclitaxel neoadjuvant regimen and bioavailability.
Aim 2 : Perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in MMTV-PyMT transgenic mouse model. This human-mimicking heterogenic model will be used to assess recurrence (after surgical excision of early mammary gland tumors) and metastasis inhibitory effects of OC-X. Expected outcomes: The intake of OC in EVOO over human history and the lack of other safe therapeutic alternatives qualify this important bioactive natural product for long-term use to prevent breast and MET-dependent cancers recurrence. Validation of an OC nutraceutical product will facilitate its commercialization for long-term use to prevent recurrence in BC patients and survivors.
Triple negative breast cancer patients have poor recurrence-free and overall survival rates, and therapeutic options are limited. Preliminary studies validated the olive oil phenolic oleocanthal as potential natural product to control breast cancer. The proposed project will test the efficacy of a novel oleocanthal powder formulation that sustained its chemical stability in preventing or suppressing triple negative breast cancer progression and recurrence in two distinct and relevant mouse models.