KEGG   DISEASE: Prostate cancer
Entry
H00024                      Disease                                
Name
Prostate cancer
  Subgroup
Hereditary prostate cancer [DS:H02530]
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.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Malignant neoplasms, except primary neoplasms 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
Pathway-based classification of diseases [BR:br08402]
 Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H00024  Prostate cancer
Tumor markers [br08442.html]
 H00024
Cancer-associated carbohydrates [br08441.html]
 H00024
Disease
pathway
hsa05215  Prostate cancer
Network
nt06272 Prostate cancer
nt06515 Regulation of kinetochore-microtubule interactions
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]
MAD1L1 (somatic mutation) [HSA:8379] [KO:K06679]
KLF6 (somatic mutation) [HSA:1316] [KO:K09207]
MXI1 (somatic mutation) [HSA:4601] [KO:K09114]
ZFHX3 (somatic mutation) [HSA:463] [KO:K09378]
Drug
Estradiol valerate [DR:D01413]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Cabazitaxel acetonate [DR:D10452]
Mitoxantrone hydrochloride [DR:D02166]
Olaparib [DR:D09730] (BRCA-mutated)
Talazoparib tosylate [DR:D10733] (HRR gene-mutated)
Estramustine phosphate sodium [DR:D02398]
Estramustine phosphate sodium hydrate [DR:D06397]
Leuprolide acetate [DR:D00989]
Leuprolide mesylate [DR:D12337]
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]
Relugolix [DR:D10888]
Sipuleucel-T [DR:D06644]
Radium Ra 223 dichloride [DR:D10398]
Lutetium Lu 177 vipivotide tetraxetan [DR:D12335] (PSMA positive)
Estrogens, esterified [DR:D04071]
Other DBs
ICD-11: 2C82
ICD-10: C61
OMIM: 176807
Reference
  Authors
Nelson WG, De Marzo AM, Isaacs WB.
  Title
Prostate cancer.
  Journal
N Engl J Med 349:366-81 (2003)
DOI:10.1056/NEJMra021562
Reference
  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
Nat Rev Cancer 7:256-69 (2007)
DOI:10.1038/nrc2090
Reference
  Authors
Abate-Shen C, Shen MM.
  Title
Molecular genetics of prostate cancer.
  Journal
Genes Dev 14:2410-34 (2000)
DOI:10.1101/gad.819500
Reference
  Authors
Porkka KP, Visakorpi T.
  Title
Molecular mechanisms of prostate cancer.
  Journal
Eur Urol 45:683-91 (2004)
DOI:10.1016/j.eururo.2004.01.012
Reference
  Authors
Brenner JC, Chinnaiyan AM
  Title
Translocations in epithelial cancers.
  Journal
Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005
Reference
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
Reference
PMID:9498904
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
DOI:10.1023/a:1018465507029
Reference
  Authors
Tsukasaki K, Miller CW, Greenspun E, Eshaghian S, Kawabata H, Fujimoto T, Tomonaga M, Sawyers C, Said JW, Koeffler HP
  Title
Mutations in the mitotic check point gene, MAD1L1, in human cancers.
  Journal
Oncogene 20:3301-5 (2001)
DOI:10.1038/sj.onc.1204421
Reference
  Authors
Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM, Ferrari AC, Martignetti JA, Friedman SL
  Title
KLF6, a candidate tumor suppressor gene mutated in prostate cancer.
  Journal
Science 294:2563-6 (2001)
DOI:10.1126/science.1066326
Reference
PMID:7773287
  Authors
Eagle LR, Yin X, Brothman AR, Williams BJ, Atkin NB, Prochownik EV
  Title
Mutation of the MXI1 gene in prostate cancer.
  Journal
Nat Genet 9:249-55 (1995)
DOI:10.1038/ng0395-249
Reference
  Authors
Sun X, Frierson HF, Chen C, Li C, Ran Q, Otto KB, Cantarel BL, Vessella RL, Gao AC, Petros J, Miura Y, Simons JW, Dong JT
  Title
Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer.
  Journal
Nat Genet 37:407-12 (2005)
DOI:10.1038/ng1528
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