Entry |
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Name |
Prostate cancer |
Description |
Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.
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Category |
Cancer
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Brite |
Human diseases [BR:br08402]
Cancers
Cancers of male genital organs
H00024 Prostate cancer
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of male genital organs
2C82 Malignant neoplasms of prostate
H00024 Prostate cancer
Tumor markers [br08442.html]
H00024
Cancer-associated carbohydrates [br08441.html]
H00024
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Pathway |
hsa05202 | Transcriptional misregulation in cancer |
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Network |
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Element |
N00052 | Mutation-inactivated PTEN to PI3K signaling pathway |
N00082 | Loss of NKX3-1 to PI3K signaling pathway |
N00084 | Amplified AR to androgen receptor signaling pathway |
N00085 | Mutation-activated AR to androgen receptor signaling pathway |
N00093 | Loss of CDKN1B to p27-cell cycle G1/S |
N00128 | TMPRSS2-ERG fusion to transcriptional activation |
N00129 | TMPRSS2-ERG fusion to transcriptional repression |
N00130 | TMPRSS2-ETV5 fusion to transcriptional activation |
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Gene |
AR (amplification, mutation) [HSA: 367] [KO: K08557]
CDKN1B (allelic loss) [HSA: 1027] [KO: K06624]
NKX3.1 (allelic loss) (decreased expression) [HSA: 4824] [KO: K09348]
PTEN (allelic loss) [HSA: 5728] [KO: K01110]
GSTP1 (hypermethylation) [HSA: 2950] [KO: K23790]
TMPRSS2-ERG (translocation) [HSA: 2078] [KO: K09435]
TMPRSS2-ETV1 (translocation) [HSA: 2115] [KO: K09431]
TMPRSS2-ETV4 (translocation) [HSA: 2118] [KO: K15592]
TMPRSS2-ETV5 (translocation) [HSA: 2119] [KO: K15593]
SLC45A3-ETV1 (translocation) [HSA: 2115] [KO: K09431]
SLC45A3-ELK4 (translocation) [HSA: 2005] [KO: K04376]
DDX5-ETV4 (translocation) [HSA: 2118] [KO: K15592]
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Carcinogen |
Cadmium and cadmium compounds [CPD: C01413]
Chimney sweeping
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Drug |
Estradiol valerate [DR: D01413]
Docetaxel [DR: D07866]
Docetaxel [DR: D02165]
Cabazitaxel acetonate [DR: D10452]
Mitoxantrone hydrochloride [DR: D02166]
Olaparib [DR: D09730] (HRR gene-mutataed)
Estramustine phosphate sodium [DR: D02398]
Estramustine phosphate sodium hydrate [DR: D06397]
Leuprolide acetate [DR: D00989]
Goserelin acetate [DR: D00573]
Triptorelin pamoate [DR: D06248]
Histrelin acetate [DR: D02116]
Flutamide [DR: D00586]
Nilutamide [DR: D00965]
Bicalutamide [DR: D00961]
Enzalutamide [DR: D10218]
Apalutamide [DR: D11040]
Darolutamide [DR: D11045]
Degarelix acetate [DR: D09400]
Abiraterone acetate [DR: D09701]
Sipuleucel-T [DR: D06644]
Radium Ra 223 dichloride [DR: D10398]
Estrogens, esterified [DR: D04071]
Relugolix [DR: D10888]
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Comment |
ICD-O: 8140/3, Tumor type: Adenocarcinoma (acinar)
ICD-O: 8148/2, Tumor type: Prostatic intraepithelial neoplasia, glade III (PIN III)
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Other DBs |
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Reference |
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Authors |
Nelson WG, De Marzo AM, Isaacs WB. |
Title |
Prostate cancer. |
Journal |
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Reference |
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Authors |
De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG. |
Title |
Inflammation in prostate carcinogenesis. |
Journal |
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Reference |
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Authors |
Abate-Shen C, Shen MM. |
Title |
Molecular genetics of prostate cancer. |
Journal |
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Reference |
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Authors |
Porkka KP, Visakorpi T. |
Title |
Molecular mechanisms of prostate cancer. |
Journal |
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Reference |
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Authors |
Brenner JC, Chinnaiyan AM |
Title |
Translocations in epithelial cancers. |
Journal |
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Reference |
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Authors |
Luch A. |
Title |
Nature and nurture - lessons from chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
Boffetta P, Jourenkova N, Gustavsson P. |
Title |
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. |
Journal |
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LinkDB |
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