Supplementary Figure 3 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. 3 shows Differentially Expressed Gene Signatures (DEGs) based on next-gene sequencing (mRNA sequencing) for ARLow/mCRPC/NEPC (PC-3DU145), ARLow/mCSPC/NEPC taxane resistant (DUTXR and PC-3TXR) PCa cell lines. IPA predicted key pathways based on DEGs between Taxane resistant and sensitivity. Fig. 3A. Differentially expressed gene Signature was identified among DEGs for ARLow/mCRPC/NEPC (PC-3DU145), ARLow/mCSPC/NEPC taxane-resistant (DUTXR and PC-3TXR) PCa cell lines. Venn diagrams represent unique and common DEGs for ARLow/mCRPC/NEPC (PC-3, DU145), and ARLow/mCSPC/NEPCtaxane-resistant (DUTXR and PC-3TXR) cell lines. Fig. 3B. IPA predicted key pathways based on DEGs between Taxane resistant and sensitivity. Cluster 2 (IPA predicted activation of PPARA), Cluster 4 (ERK/MAPK signaling, MSP-RON Signaling, upregulation of FOXM1, ESR1, CEBPB, XBP1, and NPM1), Cluster 6 (ATM signaling, and MYC).

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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.

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Keywords

Genitourinary Cancers Prostate cancer Single Cell Technologies Drug Resistance Translational Research Chemotherapy Combination chemotherapy Small Molecule Agents Topoisomerase agents Tubulin agents

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