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  Indian J Med Microbiol
 

Figure 1: Model of therapy-induced prostate cancer cell lineage plasticity. Treatment of adenocarcinoma with ADT or AR-targeted therapy ultimately leads to therapy resistance through multiple mechanisms. Notably, adenocarcinoma cells can transdifferentiate into AR-negative/NE-negative or AR-negative/NE-positive tumor types or can rely on AR bypass signaling and AR mutation to develop castration resistant adenocarcinoma. ADT: androgen deprivation therapy; AR: androgen receptor; AURKA: aurora kinase A; BRN2: brain-specific homeobox/POU domain protein 2; CGA: chromogranin A; EZH2: enhancer of zeste homolog 2; FGF: fibroblast growth factor; FOXA1: forkhead box protein A1; FOXA2: forkhead box protein A2; GR: glucocorticoid receptor; NE: neuroendocrine; NKX3.1: NK3 homeobox 1; NSE: neuron-specific enolase; MAPK: mitogen-activated protein kinases; MYCN: neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene; PSA: prostate-specific antigen; PTEN: phosphatase and tensin homolog; RB1: retinoblastoma 1; SOX: sex-determining region Y-box; SRRM2: serine/arginine repetitive matrix 2; SYP: synaptophysin; TP53: tumor protein p53.

Figure 1: Model of therapy-induced prostate cancer cell lineage plasticity. Treatment of adenocarcinoma with ADT or AR-targeted therapy ultimately leads to therapy resistance through multiple mechanisms. Notably, adenocarcinoma cells can transdifferentiate into AR-negative/NE-negative or AR-negative/NE-positive tumor types or can rely on AR bypass signaling and AR mutation to develop castration resistant adenocarcinoma. ADT: androgen deprivation therapy; AR: androgen receptor; AURKA: aurora kinase A; BRN2: brain-specific homeobox/POU domain protein 2; CGA: chromogranin A; EZH2: enhancer of zeste homolog 2; FGF: fibroblast growth factor; FOXA1: forkhead box protein A1; FOXA2: forkhead box protein A2; GR: glucocorticoid receptor; NE: neuroendocrine; NKX3.1: NK3 homeobox 1; NSE: neuron-specific enolase; MAPK: mitogen-activated protein kinases; MYCN: neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene; PSA: prostate-specific antigen; PTEN: phosphatase and tensin homolog; RB1: retinoblastoma 1; SOX: sex-determining region Y-box; SRRM2: serine/arginine repetitive matrix 2; SYP: synaptophysin; TP53: tumor protein p53.