Abstract 711: Elimination of multi-drug-resistant breast cancer cells using combination of high-intensity focused ultrasound and low-dose generic chemotherapeutic

Abstract

Abstract PURPOSE Despite medical advances, multidrug-resistant (MDR) breast cancers continue to challenge the patients. In this study, we seek to evaluate a new strategy in which the combination of High-Intensity Focused Ultrasound (HIFU) and low-dose generic chemotherapeutic is utilized to attack MDR breast cancer cells. METHOD This strategy, motivated by clinical trials in which HIFU was used to treat breast fibroadenoma, led to the in vitro study during which human triple-negative breast cancer stem cell line BT-549 (ATCC), known for resistance to Docetaxel (DTX), was paradoxically treated with low-dose DTX. Day 1: Each data sample consisted of ∼10K cells grown inside a well of 8-well glass slides (Lab-Tek). Each slide was then filled with growth media, sealed, submerged in 37ºC degassed water bath and secured onto a fixture. The targets for HIFU therapy are the center points of the 4 quadrants of each well's base. The constant HIFU parameters for each slide were acoustic pressure 5MPa, repetition rate 1Hz, focal-zone depth and 30 sec/sonication/center point while duty cycle (DC) ranged 0-50% among slides. After HIFU treatment, the slides were incubated for 24h. Day 2: Cell media for each slide was replaced with fresh media containing [DTX] 0-4 nM prior to repeating HIFU procedure from day 1. Day 4: After 48h of exposure to DTX, cell survivability study was performed to determine the contribution of HIFU-mediated necrosis as well as necrosis mediated by low [DTX] (versus apoptosis by very high [DTX]). RESULTS Cell survivability decreased by increasing [DTX] or DC. In DTX-only group (DC 0%), average survivability was 42.8% (n = 7) for [DTX] 1nM while in HIFU-only group ([DTX] 0 nM), average survivability was 25.1% (n = 7) at DC 30%. In contrast, there was virtually no survivability of breast cancer stem cells for the combination of [DTX] 1nM and DC ≥ 30%. CONCLUSION The combination of HIFU and low-dose Docetaxel was successful in virtually eliminating MDR breast cancer cells in 4 days. in vitro Treatment of Triple-Negative Breast Cancer Stem Cells Using HIFU-Docetaxel Combination[Docetaxel], (nM)0 (HIFU only)0.250.5124Average Cell Survivability (%) on day 4; DC 0% (Docetaxel only)100.084.553.042.829.514.9Average Cell Survivability (%) on day 4; DC 30%25.12.22.81.71.53.8Independent t-test p-value (n = 7)0.0034680.0036640.0200840.0017810.0019270.00116Note: Our data suggests that, in principle, drug resistance may be reversible and that a combination of HIFU and a low-dose generic chemotherapeutic may be a promising alternative to existing treatments (multidrug regimen, surgery or radiotherapy) against other MDR cancers. In addition to high efficacy within a relatively short time, the minimal/no side effects and low cost from using low-dose generic chemotherapeutic may pave the way toward a paradigm shift in near-future cancer treatments. Citation Format: Howard Q. Vo, Yoo-Shin Kim, Brian E. O'Neill. Elimination of multi-drug-resistant breast cancer cells using combination of high-intensity focused ultrasound and low-dose generic chemotherapeutic. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 711. doi:10.1158/1538-7445.AM2015-711