PMID- 10363963
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20220317
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 11
DP  - 1999 Jun 1
TI  - Selection for androgen receptor mutations in prostate cancers treated with
      androgen antagonist.
PG  - 2511-5
AB  - The role of androgen receptor (AR) mutations in androgen-independent prostate
      cancer (PCa) was determined by examining AR transcripts and genes from a large
      series of bone marrow metastases. Mutations were found in 5 of 16 patients who
      received combined androgen blockade with the AR antagonist flutamide, and these
      mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant 
      AR found among 17 patients treated with androgen ablation monotherapy was not
      flutamide stimulated. Patients with flutamide-stimulated AR mutations responded
      to subsequent treatment with bicalutamide, an AR antagonist that blocks the
      mutant ARs. These findings demonstrate that AR mutations occur in response to
      strong selective pressure from flutamide treatment.
FAU - Taplin, M E
AU  - Taplin ME
AD  - University of Massachusetts Cancer Center, Worcester 01655, USA.
FAU - Bubley, G J
AU  - Bubley GJ
FAU - Ko, Y J
AU  - Ko YJ
FAU - Small, E J
AU  - Small EJ
FAU - Upton, M
AU  - Upton M
FAU - Rajeshkumar, B
AU  - Rajeshkumar B
FAU - Balk, S P
AU  - Balk SP
LA  - eng
GR  - R01-CA65647/CA/NCI NIH HHS/United States
GR  - U10-CA78967/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Androgen Antagonists)
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Codon)
RN  - 0 (Nitriles)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Tosyl Compounds)
RN  - 76W6J0943E (Flutamide)
RN  - A0Z3NAU9DP (bicalutamide)
SB  - IM
MH  - Androgen Antagonists/*therapeutic use
MH  - Anilides/therapeutic use
MH  - Antineoplastic Agents, Hormonal/*therapeutic use
MH  - Biopsy
MH  - Bone Marrow/pathology
MH  - Bone Marrow Neoplasms/*genetics/secondary
MH  - Codon/genetics
MH  - DNA Mutational Analysis
MH  - Flutamide/therapeutic use
MH  - Humans
MH  - Male
MH  - Mutation/*genetics
MH  - Neoplasms, Hormone-Dependent/chemistry/drug therapy/*genetics/pathology
MH  - Nitriles
MH  - Prostatic Neoplasms/chemistry/drug therapy/*genetics/pathology
MH  - Receptors, Androgen/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tosyl Compounds
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Jun 1;59(11):2511-5.