Androgen receptor and prostate cancer stem cells: biological mechanisms and clinical implications.
Prostate cancer (PCa) contains phenotypically and functionally distinct cells, and this cellular heterogeneity poses clinical challenges as the distinct cell types likely respond differently to various therapies. Clonal evolution, driven by genetic instability, and intraclonal cancer cell diversification, driven by cancer stem cells (CSCs), together create tumor cell heterogeneity. In this review, we first discuss PCa stem cells (PCSCs) and heterogeneity of androgen receptor (AR) expression in primary, metastatic, and treatment-failed PCa. Based on literature reports and our own studies, we hypothesize that, whereas PCSCs in primary and untreated tumors and models are mainly AR(-), PCSCs in CRPCs could be either AR(+) or AR(-/lo). We illustrate the potential mechanisms AR(+) and AR(-) PCSCs may employ to propagate PCa at the population level, mediate therapy resistance, and metastasize. As a result, targeting AR alone may not achieve long-lasting therapeutic efficacy. Elucidating the roles of AR and PCSCs should provide important clues to designing novel personalized combinatorial therapeutic protocols targeting both AR(+) and AR(-) PCa cells.
Department of Epigenetics and Molecular CarcinogenesisUniversity of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USAProgram in Molecular CarcinogenesisUniversity of Texas Graduate School of Biomedical Sciences, Houston, Texas, USACancer Stem Cell InstituteResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Department of Epigenetics and Molecular CarcinogenesisUniversity of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USAProgram in Molecular CarcinogenesisUniversity of Texas Graduate School of Biomedical Sciences, Houston, Texas, USACancer Stem Cell InstituteResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Qu
Q
Deng
Department of Epigenetics and Molecular CarcinogenesisUniversity of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USAProgram in Molecular CarcinogenesisUniversity of Texas Graduate School of Biomedical Sciences, Houston, Texas, USACancer Stem Cell InstituteResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Department of Epigenetics and Molecular CarcinogenesisUniversity of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USAProgram in Molecular CarcinogenesisUniversity of Texas Graduate School of Biomedical Sciences, Houston, Texas, USACancer Stem Cell InstituteResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Department of Epigenetics and Molecular CarcinogenesisUniversity of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USAProgram in Molecular CarcinogenesisUniversity of Texas Graduate School of Biomedical Sciences, Houston, Texas, USACancer Stem Cell InstituteResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China dtang@mdanderson.org.
Dean G
DG
Tang
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction
C410798:AR protein, human; C000607144:AR protein, mouse; D000728:Androgens; D009363:Neoplasm Proteins; D011944:Receptors, Androgen
androgen receptor; cancer stem cells; castration-resistant prostate cancer; prostate cancer; prostate cancer stem cells