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Houston, TX, United States

Landis M.D.,The Methodist Cancer Center | Lehmann B.D.,Vanderbilt University | Pietenpol J.A.,Vanderbilt University | Chang J.C.,The Methodist Cancer Center | Chang J.C.,The New School
Breast Cancer Research | Year: 2013

Despite improved detection and reduction of breast cancer-related deaths over the recent decade, breast cancer remains the second leading cause of cancer death for women in the US, with 39,510 women expected to succumb to metastatic disease in 2012 alone (American Cancer Society, Cancer Facts &Figures 2012. Atlanta: American Cancer Society; 2012). Continued efforts in classification of breast cancers based on gene expression profiling and genomic sequencing have revealed an underlying complexity and molecular heterogeneity within the disease that continues to challenge therapeutic interventions. To successfully identify and translate new treatment regimens to the clinic, it is imperative that our preclinical models recapitulate this complexity and heterogeneity. In this review article, we discuss the recent advances in development and classification of patient-derived human breast tumor xenograft models that have the potential to facilitate the next phase of drug discovery for personalized cancer therapy based on the unique driver signaling pathways in breast tumor subtypes. © 2013 BioMed Central Ltd.

Dave B.,The Methodist Cancer Center | Landis M.D.,The Methodist Cancer Center | Dobrolecki L.E.,The Methodist Cancer Center | Wu M.-F.,Baylor College of Medicine | And 7 more authors.
PLoS ONE | Year: 2012

Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24-/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24-/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors. © 2012 Dave et al.

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