The development of androgen-independent prostate cancer

  title={The development of androgen-independent prostate cancer},
  author={Brian J Feldman and David Feldman},
  journal={Nature Reviews Cancer},
The normal prostate and early-stage prostate cancers depend on androgens for growth and survival, and androgen ablation therapy causes them to regress. Cancers that are not cured by surgery eventually become androgen independent, rendering anti-androgen therapy ineffective. But how does androgen independence arise? We predict that understanding the pathways that lead to the development of androgen-independent prostate cancer will pave the way to effective therapies for these, at present… 
Androgen Action in Prostate Cancer
This review summarizes the current information regarding the role of androgens in prostate cancer and recommends androgen ablation as the preferred initial therapeutic approach for the treatment of advanced prostate cancer patients.
Mechanisms leading to the development of hormone-resistant prostate cancer.
Biology of castration-recurrent prostate cancer.
Mechanisms of androgen-refractory prostate cancer.
When prostate cancer is localized in the prostate, the treatment of choice is prostatectomy or irradiation, however, when the tumor relapses or is already metastatic at diagnosis, therapy is problematic.
Upregulation of the Androgen Receptor during Prostate Cancer Progression
It is reported that the androgen receptor is consistently upregulated as hormone sensitive prostate cancer changes to a hormone refractory state and that this change is intricately involved during the development of resistance to androgen ablation therapy.
Molecular basis for androgen independency in prostate cancer
This review will try to summarize the knowledge of the genetic events governing the conversion to androgen independency in prostate tumorigenesis.
Mechanisms Underlying the Development of Androgen-Independent Prostate Cancer
It is estimated that during 2005, ∼232,090 new cases of prostate cancer will be diagnosed in the United States and 30,350 menwill be diagnosed with prostate cancer.
Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity
The role of the androgen receptor in the progression of androgen‐dependent human prostate cancer cells to androgen-independent and androgens‐insensitive phenotypes is unclear.


LNCaP progression model of human prostate cancer: Androgen‐independence and osseous metastasis
One of the sublines, C4‐2, was found to be AI, highly tumorigenic, and metastatic, having a proclivity for metastasis to the bone.
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor
It is shown that in CaP cells from a patient who failed androgen ablation therapy, a doubly mutated AR functioned as a high-affinity cortisol/cortisone receptor (ARccr), demonstrating a previously unknown mechanism for the androgen-independent growth of advanced CaP.
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It is concluded that prostate cancers contain heterogeneous mixtures of cells that vary in their dependence on androgen for growth and survival and that treatment with antiandrogen therapy provides selective pressure and alters the relative frequency of these cells, thereby leading to outgrowths of androgen-independent cancers.
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Her-2-neu expression appears to increase with progression to androgen independence, and therapeutic targeting of this tyrosine kinase in prostate cancer may be warranted.
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Missense mutations in the AR gene identified in prostate cancer that collocate to discrete regions of the receptor contribute to altered androgen signaling and provide a potential mechanism to explain the reemergence of tumor growth during the course of hormone ablation therapies.
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By modulating the response to low doses of androgen, a tyrosine kinase receptor can restore androgen receptor function to prostate cancer cells, a finding directly related to the clinical progression of prostate cancer.
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Functional studies of two of the mutant androgen receptors demonstrated that they could be activated by progesterone and estrogen, and may provide a selective growth advantage after androgen ablation.
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  • L. Mendelsohn
  • Biology
    Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques
  • 2000
Progress in this direction has been realized with the recent synthesis of non-steroidal androgen agonists that may have tissue-selective effects.
In vivo amplification of the androgen receptor gene and progression of human prostate cancer
This work has identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene.