KEGG   DISEASE: Prostate cancer
H00024                      Disease                                

Prostate cancer
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.
Human diseases [BR:br08402]
  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]
Cancer-associated carbohydrates [br08441.html]
hsa05215  Prostate cancer
hsa05202  Transcriptional misregulation in cancer
hsa05206  MicroRNAs in cancer
nt06272  Prostate cancer
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
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]
Cadmium and cadmium compounds [CPD:C01413]
Chimney sweeping
Estradiol valerate [DR:D01413]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Cabazitaxel acetonate [DR:D10452]
Mitoxantrone hydrochloride [DR:D02166]
Estramustine phosphate sodium [DR:D02398]
Estramustine phosphate sodium hydrate [DR:D06397]
Olaparib [DR:D09730] (HRR gene-mutataed)
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]
ICD-O: 8140/3, Tumor type: Adenocarcinoma (acinar)
ICD-O: 8148/2, Tumor type: Prostatic intraepithelial neoplasia, glade III (PIN III)
Other DBs
ICD-11: 2C82
ICD-10: C61
PMID:12878745 (gene, tumor type)
Nelson WG, De Marzo AM, Isaacs WB.
Prostate cancer.
N Engl J Med 349:366-81 (2003)
PMID:17384581 (gene, tumor type)
De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG.
Inflammation in prostate carcinogenesis.
Nat Rev Cancer 7:256-69 (2007)
PMID:11018010 (tumor type)
Abate-Shen C, Shen MM.
Molecular genetics of prostate cancer.
Genes Dev 14:2410-34 (2000)
Porkka KP, Visakorpi T.
Molecular mechanisms of prostate cancer.
Eur Urol 45:683-91 (2004)
Brenner JC, Chinnaiyan AM
Translocations in epithelial cancers.
Biochim Biophys Acta 1796:201-15 (2009)
PMID:15660110 (carcinogen)
Luch A.
Nature and nurture - lessons from chemical carcinogenesis.
Nat Rev Cancer 5:113-25 (2005)
PMID:9498904 (carcinogen)
Boffetta P, Jourenkova N, Gustavsson P.
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
Cancer Causes Control 8:444-72 (1997)

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