Abstract LB-401: The chemosensitizing properties of iniparib in combination with DNA-damaging agents in the MDA-MB-468(−) triple-negative breast cancer (TNBC) cell line

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL BACKGROUND : Iniparib (BSI-201) has demonstrated promising efficacy and safety in the treatment of patients with metastatic triple-negative breast cancer (TNBC). The addition of iniparib to gemcitabine (G) and carboplatin (C) improved the clinical benefit rate from 34% to 56% ( P = 0.01) and the overall response rate from 32% to 52% ( P = 0.02) in a phase II clinical study (O'Shaughnessy et al. N Engl J Med . 2011).We investigated the chemosensitizing properties of iniparib with irinotecan (I) or ionizing radiation (IR). METHODS : The chemosensitizing properties of a single dose of iniparib combined with I or IR were evaluated in TNBC MDA-MB-468 breast carcinoma cells. Cell proliferation was evaluated with FACS-based cell cycle analysis, including DNA staining and bromodeoxyuridine incorporation. RESULTS : FACS analysis showed that in TNBC MDA-MB-468 breast carcinoma cells iniparib potentiated cell cycle arrest induced by I, with cells arrested in S and G2/M phases, or potentiated cell cycle arrest induced by IR, with cells arrested mostly in G2/M, at 72 hours after treatment ([Table 1][1]). CONCLUSIONS : These data demonstrate the potentiation of the antiproliferative activity of I and IR by iniparib in TNBC MDA-MB-468 breast carcinoma cells. These data support investigation of iniparib in combination with these DNA-damaging agents in clinical studies. ![Figure][2] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-401. doi:10.1158/1538-7445.AM2011-LB-401 [1]: #F1 [2]: pending:yes