Supplementary Figure 2 from Metronomic Administration of Topotecan Alone and in Combination with Docetaxel Inhibits Epithelial–mesenchymal Transition in Aggressive Variant Prostate Cancers

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posted on 2023-07-19, 14:20 authored by Taraswi Mitra Ghosh, Suman Mazumder, Joshua Davis, Jyoti Yadav, Ayuba Akinpelu, Ahmed Alnaim, Harish Kumar, Razan Waliagha, Allison E. Church Bird, Soroush Rais-Bahrami, R. Curtis Bird, Panagiotis Mistriotis, Amarjit Mishra, Clayton C. Yates, Amit K. Mitra, Robert D. Arnold

Supplementary Fig. 2 shows Ingenuity pathway analysis (IPA) predictions for European American/ Caucasian American (EA/CA) ARHigh/mCSPC (LNCaP, VCAP, 22RV1), ARLow/mCRPC/NEPC (PC-3, PC-3M, DU145) and African American (AA) ARHigh/mCSPC (MDA-Pca-2b) PCa cell lines as well as normal prostate cell lines RWPE1 and RWPE2. IPA predicted A) Diseases and biological pathways for development of ARLow/mCRPC/NEPC. Major pathways are cell movement, morbidity, mortality, migration, invasion, survival, viability and development of vasculature- vasculogenesis and angiogenesis. B) Causal network pathway for development of ARLow/mCRPC/NEPC, which include oxidative phosphorylation, p70S6K, unfolded response, TREM1 signaling, NF-kB signaling, ERK5 signaling, IL-8 signaling, BAG2 signaling, Integrin signaling and VEGF signaling. C) IPA predicted HIF1α and EMT as key pathways associated with PCa development in African Americans (AA).

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ARTICLE ABSTRACT

The utilization of metronomic-like dosing regimens of topotecan alone and in combination with DTX resulted in the suppression of makers associated with EMT and stem-like cell populations in AVPC models. The identification of molecular signatures and their potential to serve as novel biomarkers for monitoring treatment efficacy and disease progression response to treatment efficacy and disease progression were achieved using bulk RNA-seq and single-cell-omics methodologies.