Cited by 107Prostate Cancer Treatment and ResearchProstate Cancer Diagnosis and TreatmentHormonal and reproductive studies

The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.

Castration-recurrent prostate cancer is not androgen-independent.

Mohler, James L.·2008·Advances in experimental medicine and biology

DOI 10.1007/978-0-387-69080-3_21

Open this paper in CoChat — free account

Abstract

An American man is diagnosed with prostate cancer (PC) every 3 min and dies from the disease every 17 min. Although androgen receptor (AR) expression is diminished following androgen deprivation therapy (ADT) that induces clinical remission in most patients, castration-recurrent PC expresses levels of AR protein similar to those found in androgen-stimulated PC and benign prostate. This observation suggests that the AR may be as important for growth regulation in castration-recurrent PC, as it is in androgen-stimulated PC and benign hyperplasia. Neither ligand-independence, point mutations, glutamine and/or glycine repeat expansion nor amplification have explained AR activation in most cases of castration-recurrent PC. Castration-recurrent PC tissue has levels of testosterone (T) similar to androgen-stimulated benign prostate and levels of dihydrotestosterone (DHT), the most active androgen for AR activation that are approximately 10% of androgen-stimulated benign prostate. These levels of tissue androgens appear capable of activating the AR since prostate-specific antigen (PSA), the classic androgen-regulated gene, is expressed at similar tissue levels in castration-recurrent and androgen-stimulated PC. These startling findings suggest a paradigm shift; PC that recurs during ADT is not androgen-independent.

Integrity signals

Registry

Crossref · 10.1007/978-0-387-69080-3_21

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cancer Statistics, 2006
Jemal, A., Siegel, R. L., Ward, E. M., Murray, T., Xu, J., Smigal, C., & Thun, M. J. (2006) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.56.2.106 · Cited by 5,309
Studies on Prostatic Cancer: I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate
Huggins, C., & Hodges, C. V. (2002) · The Journal of Urology · doi:10.1016/s0022-5347(05)64820-3 · Cited by 3,856
The development of androgen-independent prostate cancer.
Feldman, B. J., & Feldman, D. (2001) · Nature reviews. Cancer · doi:10.1038/35094009 · Cited by 2,326
Molecular determinants of resistance to antiandrogen therapy
Chen, C. D., Welsbie, D. S., Tran, C., Baek, S. H., Chen, R., Vessella, R., Rosenfeld, M. G., & Sawyers, C. L. (2004) · Nature Medicine · doi:10.1038/nm972 · Cited by 2,278
In vivo amplification of the androgen receptor gene and progression of human prostate cancer
Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinänen, R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., & Kallioniemi, O.-P. (1995) · Nature Genetics · doi:10.1038/ng0495-401 · Cited by 1,484
Mutation of the Androgen-Receptor Gene in Metastatic Androgen-Independent Prostate Cancer
Taplin, M., Bubley, G. J., Shuster, T. D., Frantz, M. E., Spooner, A. E., Ogata, G. K., Keer, H. N., & Balk, S. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505253322101 · Cited by 1,243
Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Androgen-Independent Prostate Cancer
Stanbrough, M., Bubley, G. J., Ross, K., Golub, T. R., Rubin, M. A., Penning, T. M., Febbo, P. G., & Balk, S. P. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4000 · Cited by 1,082
Molecular Biology of the Androgen Receptor
Gelmann, E. P. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.10.018 · Cited by 972
Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.
Eisenberger, M. A., Blumenstein, B. A., Crawford, E. D., Miller, G., McLeod, D. G., Loehrer, P. J., Wilding, G., Sears, K., Culkin, D. J., Thompson, I. M., et al. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810083391504 · Cited by 859
Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer.
Linja, M. J., Savinainen, K., Saramäki, O. R., Tammela, T. L. J., Vessella, R. L., & Visakorpi, T. (2001) · PubMed · Cited by 762
The Androgen Axis in Recurrent Prostate Cancer
Mohler, J. L., Gregory, C. W., Ford, O. H., Kim, D., Weaver, C. M., Petrusz, P., Wilson, E. M., & French, F. S. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1146-03 · Cited by 675
Self-citation
Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941.
Huggins, C., & Hodges, C. (2002) · Journal of Urology · doi:10.1016/s0022-5347(02)80307-x · Cited by 637
A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy.
Gregory, C. W., He, B., Johnson, R. T., Ford, O. H., Mohler, J. L., French, F. S., & Wilson, E. (2001) · PubMed · Cited by 603
Self-citation
From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells
Yeh, S., Lin, H., Kang, H., Thin, T. H., Lin, M., & Chang, C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5458 · Cited by 594
Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.
Taplin, M., Bubley, G. J., Ko, Y., Small, E. J., Upton, M. P., Rajeshkumar, B. R., & Balk, S. P. (1999) · PubMed · Cited by 594
Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer
Grossmann, M. E., Huang, H., & Tindall, D. J. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.22.1687 · Cited by 548
Untitled work
(2001) · PubMed · Cited by 500
Self-citation
Testosterone and Dihydrotestosterone Tissue Levels in Recurrent Prostate Cancer
Titus, M. A., Schell, M. J., Lih, F. B., Tomer, K. B., & Mohler, J. L. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0525 · Cited by 488
Self-citation
Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone
Čulig, Z., Hobisch, A., Cronauer, M. V., Cato, A. C. B., Hittmair, A., Radmayr, C., Eberle, J., Bartsch, G., & Klocker, H. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.12.8145761 · Cited by 440
Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer
Edwards, J., Krishna, N. S., Grigor, K. M., & Bartlett, J. M. S. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601127 · Cited by 425
Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system
Čulig, Z., Hoffmann, J., Erdel, M., Eder, I. E., Hobisch, A., Hittmair, A., Bartsch, G., Utermann, G., Schneider, M. R., Parczyk, K., et al. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690684 · Cited by 410
Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence.
Tilley, W. D., Buchanan, G., Hickey, T. E., & Bentel, J. M. (1996) · PubMed · Cited by 395
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence
Taplin, M., & Balk, S. P. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10653 · Cited by 392
Androgen receptors in endocrine‐therapy‐resistant human prostate cancer
van der Kwast, T., Schalken, J. A., de Winter, J. A. R., van Vroonhoven, J. C. C., Mulder, E., Boersma, W. J. A., & Trapman, J. (1991) · International Journal of Cancer · doi:10.1002/ijc.2910480206 · Cited by 387
Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways.
Ueda, T., Bruchovsky, N., & Sadar, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108255200 · Cited by 381
Dehydroepiandrosterone Activates Mutant Androgen Receptors Expressed in the Androgen-Dependent Human Prostate Cancer Xenograft CWR22 and LNCaP Cells
Tan, J.-A., Sharief, Y., Hamil, K. G., Gregory, C. W., Zang, D.-Y., Sar, M., Gumerlock, P. H., White, R. D., Pretlow, T. G., Harris, S. E., et al. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.4.9906 · Cited by 375
Self-citation
Untitled work
(1994) · PubMed Central · Cited by 328
Maximum androgen blockade in advanced prostate cancer: an overview of 22 randomised trials with 3283 deaths in 5710 patients
Prostate Cancer Trialists' Collaborative Group (1995) · The Lancet · doi:10.1016/s0140-6736(95)92163-x · Cited by 320
Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells.
Ueda, T., Mawji, N. R., Bruchovsky, N., & Sadar, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203313200 · Cited by 311
Distant metastases from prostatic carcinoma express androgen receptor protein.
Hobisch, A., CULIG, Z., Radmayr, C., Bartsch, G., Klocker, H., & Hittmair, A. (1995) · PubMed · Cited by 283
New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen.
Labrie, F., Dupont, A., Bèlanger, A., Cusan, L., Lacourcière, Y., Monfette, G., LaBerge, J., Emond, J., Fazekas, A. T. A., Raynaud, J., et al. (1982) · PubMed · Cited by 276
Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues.
Simard, J., Luthy, I., Guay, J., Bélanger, A., & Labrie, F. (1986) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(86)90132-2 · Cited by 256
Persistent Intraprostatic Androgen Concentrations after Medical Castration in Healthy Men
Page, S. T., Lin, D. W., Mostaghel, E. A., Hess, D. L., True, L. D., Amory, J. K., Nelson, P. S., Matsumoto, A. M., & Bremner, W. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0968 · Cited by 229
MAXIMUM ANDROGEN BLOCKADE IN ADVANCED PROSTATE-CANCER - AN OVERVIEW OF 22 RANDOMIZED TRIALS WITH 3283 DEATHS IN 5710 PATIENTS
Dalesio, O., VANTINTEREN, H., Denis, L., Schröder, F. H., Blumenstein, B. A., Godwin, J., & Peto, R. (1995) · The Lancet · Cited by 229
Activated Tyrosine Kinase Ack1 Promotes Prostate Tumorigenesis: Role of Ack1 in Polyubiquitination of Tumor Suppressor Wwox
Mahajan, N. P., Whang, Y. E., Mohler, J. L., & Earp, H. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1127 · Cited by 228
Self-citation
The Influence of Androgen Deprivation Therapy on Dihydrotestosterone Levels in the Prostatic Tissue of Patients with Prostate Cancer
Nishiyama, T., Hashimoto, Y., & Takahashi, K. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0913 · Cited by 224
Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men.
Bélanger, B., Bélanger, A., Labrie, F., Dupont, A., Cusan, L., & Monfette, G. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90514-1 · Cited by 212
Hormones and prostate cancer: Current perspectives and future directions
Hsing, A. W., Reichardt, J. K. V., & Stanczyk, F. Z. (2002) · The Prostate · doi:10.1002/pros.10108 · Cited by 207
STEROIDS OF ADRENAL ORIGIN METABOLIZED BY HUMAN PROSTATIC TISSUE BOTH IN VIVO AND IN VITRO
Harper, M. E., Pike, A. W., Peeling, W. B., & Griffiths, K. (1974) · Journal of Endocrinology · doi:10.1677/joe.0.0600117 · Cited by 190
The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue after Androgen Deprivation Therapy and Activates Mutated Androgen Receptor
Mizokami, A., Koh, E., Fujita, H., Maeda, Y., Egawa, M., Koshida, K., Honma, S., Keller, E. T., & Namiki, M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0130 · Cited by 175
ANDROGEN RECEPTOR GENE AMPLIFICATION AT PRIMARY PROGRESSION PREDICTS RESPONSE TO COMBINED ANDROGEN BLOCKADE AS SECOND LINE THERAPY FOR ADVANCED PROSTATE CANCER
Palmberg, C., Koivisto, P. A., Kakkola, L., Tammela, T. L. J., Kallioniemi, O., & Visakorpi, T. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)66935-2 · Cited by 152
Functional analysis of 44 mutant androgen receptors from human prostate cancer.
Shi, X., Ma, A., Xia, L. P., Kung, H.-J., & White, R. D. (2002) · PubMed · Cited by 150
Prostate cancer: molecular biology of early progression to androgen independence.
Sadar, M. D., Hussain, M., & Bruchovsky, N. (1999) · Endocrine Related Cancer · doi:10.1677/erc.0.0060487 · Cited by 148
Androgen Receptor Gene Amplification and Protein Expression in Recurrent Prostate Cancer
Ford, O. H., Gregory, C. W., Kim, D., Smitherman, A. B., & Mohler, J. L. (2003) · The Journal of Urology · doi:10.1097/01.ju.0000091873.09677.f4 · Cited by 145
Self-citation
Inhibition of HER-2/neu Kinase Impairs Androgen Receptor Recruitment to the Androgen Responsive Enhancer
Liu, Y., Majumder, S., McCall, W., Sartor, C. I., Mohler, J. L., Gregory, C. W., Earp, H. S., & Whang, Y. E. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4292 · Cited by 99
Self-citation
Prevalence of androgen receptor gene mutations in latent prostatic carcinomas from Japanese men.
Takahashi, H., Furusato, M., Allsbrook, W. C., Nishii, H., Wakui, S., Barrett, J. C., & Boyd, J. A. (1995) · PubMed · Cited by 91
Amplification of the androgen receptor gene in bone metastases from hormone‐refractory prostate cancer
Brown, R. S. D., Edwards, J., Doǧan, A., Payne, H. A., Harland, S. J., Bartlett, J. M. S., & Masters, J. R. (2002) · The Journal of Pathology · doi:10.1002/path.1206 · Cited by 87
Hypoxia Increases Androgen Receptor Activity in Prostate Cancer Cells
Park, S.-Y., Kim, Y.-J., Gao, A. C., Mohler, J. L., Onate, S. A., Hidalgo, A. A., Ip, C., Park, E.-M., Yoon, S. Y., & Park, Y.-M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1341 · Cited by 81
Self-citation
Mutant androgen receptors in prostatic tumors distinguish between amino‐acid‐sequence requirements for transactivation and ligand binding
Peterziel, H., Čulig, Z., Stober, J., Hobisch, A., Radmayr, C., Bartsch, G. H., Klocker, H., & Cato, A. C. B. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910630415 · Cited by 75
Androgen Receptor Expression and Cellular Proliferation During Transition from Androgen-Dependent to Recurrent Growth after Castration in the CWR22 Prostate Cancer Xenograft
Kim, D., Gregory, C. W., French, F. S., Smith, G. J., & Mohler, J. L. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64365-9 · Cited by 71
Self-citation
Enzymes of Androgen Formation and Degradation in the Human Prostate
BARTSCH, W., Klein, H., Schiemann, U., Bauer, H. W., & Voigt, K. D. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb34282.x · Cited by 67
Steroid levels in cancer of the prostate-markers of tumour differentiation and adequacy of anti-androgen therapy
Geller, J., ALBERT, J. D., & Loza, D. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90092-x · Cited by 48
The distribution of PSA, cathepsin‐D, and pS2 in BPH and cancer of the prostate
Yang, Y., CHISHOLM, G. D., & Habib, F. K. (1992) · The Prostate · doi:10.1002/pros.2990210304 · Cited by 33
Synergistic activation of the androgen receptor by bombesin and low-dose androgen.
Dai, J., Shen, R., Sumitomo, M., Stahl, R. E., Navarro, D., Gershengorn, M. C., & Nanus, D. M. (2002) · PubMed · Cited by 31
Quantitative Estimation of Tissue Prostate Specific Antigen, Deoxyribonucleic Acid Ploidy and Cytological Grade in Fine Needle Aspiration Biopsies for Prognosis of Hormonally Treated Prostatic Carcinoma
Stege, R., Tribukait, B., Lundh, B., Carlström, K., Pousette, Å., & Hasenson, M. (1992) · The Journal of Urology · doi:10.1016/s0022-5347(17)36736-8 · Cited by 31
Apoptosis levels increase after castration in the CWR22 human prostate cancer xenograft
Smitherman, A. B., Gregory, C. W., & Mohler, J. L. (2003) · The Prostate · doi:10.1002/pros.10271 · Cited by 22
Self-citation
Mutational Analysis of the Androgen Receptor Using Laser Capture Microdissection and Direct Sequencing
Greene, S., Stockton, P., Kozyreva, O. G., Gaston, K. E., Flake, G. P., & Mohler, J. L. (2003) · Humana Press eBooks · doi:10.1385/1-59259-356-9:287 · Cited by 5
Self-citation

Sorted by citations

Androgen Signaling in Prostate CancerPreprint
Dai, C. S., Heemers, H. V., & Sharifi, N. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a030452 · Cited by 432
Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study
Schweizer, M. T., Antonarakis, E. S., Wang, H., Ajiboye, A. S., Spitz, A. N., Cao, H., Luo, J., Haffner, M. C., Yegnasubramanian, S., Carducci, M. A., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010563 · Cited by 259
Castration-resistant Prostate Cancer: From New Pathophysiology to New Treatment Targets
Chi, K. N., Bjartell, A., Dearnaley, D. P., Fred Saad, C., Schröder, F. H., Sternberg, C., TOMBAL, B. F., & Visakorpi, T. (2009) · European Urology · doi:10.1016/j.eururo.2009.06.027 · Cited by 252
Understanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer
Buttigliero, C., Tucci, M., Bertaglia, V., Vignani, F., Bironzo, P., Maïo, M. D., & Scagliotti, G. V. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2015.08.002 · Cited by 198
Nadir Testosterone Within First Year of Androgen-Deprivation Therapy (ADT) Predicts for Time to Castration-Resistant Progression: A Secondary Analysis of the PR-7 Trial of Intermittent Versus Continuous ADT
Klotz, L. H., O’Callaghan, C. J., Ding, K., Toren, P., Dearnaley, D. P., Higano, C. S., Horwitz, E. M., Malone, S. C., Goldenberg, L., Gospodarowicz, M. K., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.2973 · Cited by 168

See all 107

Authors: Mohler, J. L.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Mohler, James L.
ORCID: Mohler, James L.
Venue: Advances in experimental medicine and biology
Publisher: Springer New York
Published: 2008
Volume: 617
Pages: 223-234
ISSN: 0065-2598 (ISSN-L)
DOI: 10.1007/978-0-387-69080-3_21
OpenAlex: W202356157
Cited by: 106
References: 57
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 9 · 2013: 15 · 2012: 8
FWCI: 62.53
Type: book chapter
Language: en
Open access: closed
Locations: Advances in experimental medicine and biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: castration-resistant prostate cancer, recurrent prostate cancer, androgen receptor, androgen-independent growth, androgen deprivation therapy, dihydrotestosterone, testosterone, prostate-specific antigen, androgen receptor activation, benign prostatic hyperplasia
MeSH terms: Androgens, Humans, Male, Neoplasm Recurrence, Local, Neoplasms, Hormone-Dependent, Orchiectomy, Prostatic Neoplasms, Receptors, Androgen

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Castration-recurrent prostate cancer is not androgen-independent.

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks