Abstract PR13: Using a hypoxia-induced CSC tumor initiation model to improve predictive potential for patients with metastatic breast cancer

Abstract

Abstract About 10-20% of breast cancers are found to be triple-negative. TNBCs have a relapse pattern that is very different from hormone-positive breast cancers: the risk of relapse is much higher for the first 3-5 years but drops substantially below that of hormone-positive breast cancers after that. Therefore, preventing tumor recurrence and metastasis in high-risk TNBC patients within 3-5 years of diagnosis will dramatically improve the long-term survival of these patients. Currently, most of preclinical animal models have limited predictive clinical potential for advanced metastatic diseases. One possible explanation is that most of the pre-clinical studies focus on the therapeutic benefit of eradicating bulk tumor cells. Using a stem-like subpopulation from triple negative breast cancer (TNBC) cell lines enriched by exposing the cells to cycles of hypoxia and reoxygenation, we showed that mammary tumors initiated from this subpopulation have a high recurrence rate (100%) after the taxol treatment compared to no recurrence from taxol treated tumors initiated from the bulk cancer cells. Our model mimics the progression of recurrence-prone breast tumors with a period of dormancy before the recurrence of local and distal tumors. Molecular analysis of the treatment naïve and recurrent tumors revealed increased expression of chemoresistance-associated miRNAs in the recurred xenograft tumors. In addition, we identified new markers in the recurred xenograft tumors that are also increased in drug resistant human breast tumors compared to the treatment naïve breast tumors. Ultimately, we propose that cancer stem cell based tumor model can be used to improve the predictive potential of pre-clinical models for patients with metastatic breast tumors. This abstract is also presented as Poster A12. Citation Format: Purvi Patel, Yupo Ma, Haiyan Zhai, Jingfeng Ju, Emily Chen. Using a hypoxia-induced CSC tumor initiation model to improve predictive potential for patients with metastatic breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr PR13.