Systemic treatment of hormone refractory prostate cancer

Rübben, H.; Bex, Axel; Otto, T.

doi:10.1007/s003450000186

Cited by 11 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since androgens play an important role in progression of prostate cancer, androgen ablation and blockade of androgen action are the two most common modalities for treating prostate cancer. Although bicalutamide is one of the most widely used nonsteroidal antiandrogens for treating prostate cancer, it is highly hydrophobic and prolonged exposure leads to drug resistance, the occurrence of hormone refractory prostate cancer and an increased propensity for metastasis (32)(33)(34)(35). Since hormone refractory tumors are resistant to apoptosis and overexpress XIAP, the objective of this study was to see whether small molecule XIAP inhibitor such as embelin can be used to treat bicalutamide irresponsive tumors.…”

Section: Discussionmentioning

confidence: 99%

Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer

Danquah

Duke

et al. 2009

Pharm Res

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer

Danquah

Duke

et al. 2009

Pharm Res

View full text Add to dashboard Cite

show abstract

“…Casodex is now being used as a monotherapy due to its preservation of testosterone levels and sexual potency and has provided an attractive alternative therapeutic approach to surgical intervention [Kolvenbag and Nash, 1999]. However, tumors treated with anti‐androgens frequently become hormone refractory and have an increase propensity for metastasis [Grossmann et al, 2001; Kish et al, 2001; Knox and Moore, 2001; Rubben et al, 2001]. Resistant to anti‐androgen therapy has been attributed to the intrinsic ability of tumor cells to abrogate the cell death process induced by the anti‐androgens.…”

Section: Anti‐androgens In Prostate Cancer Therapymentioning

confidence: 99%

Emergence of metastatic hormone‐refractory disease in prostate cancer after anti‐androgen therapy

Lee

Tenniswood

2004

J of Cellular Biochemistry

View full text Add to dashboard Cite

The anti-androgens used in prostate cancer therapy have been designed to interfere with the normal androgen receptor (AR)-mediated processes that ensure prostate cell survival, triggering tumor cells to undergo programmed cell death. While anti-androgens were originally designed to treat advanced disease, they have recently been used to debulk organ-confined prostate tumors, to improve positive margins prior to surgery, and for chemoprevention in patients at high risk for prostate cancer. However, tumors treated with anti-androgens frequently become hormone refractory and acquire a more aggressive phenotype. Progression toward metastatic hormone-refractory disease has often been regarded as the outgrowth of a small number of hormone-independent cells that emerge from a hormone-dependent tumor during anti-androgen treatment by natural selection. While a number of selective advantages have recently been identified, there is also considerable evidence suggesting that the progression toward metastatic hormone-refractory disease is an dynamic process which involves abrogation of programmed cell death as a result of the attenuation of DNA fragmentation and maintenance of mitochondrial membrane potential in tumor cells; the upregulation of stromal-mediated growth factor signaling pathways; and the upregulation of extracellular matrix (ECM) protease expression.

show abstract

“…2 However, tumors treated with antiandrogens ultimately become hormone refractory and have an increase propensity for metastasis. [3][4][5][6] Apoptosis is usually manifested by one of two major execution pathways downstream of death signals: the death receptor-mediated pathway, often referred to as the extrinsic pathway, and the mitochondrial pathway or intrinsic pathway. 7 The death receptor-mediated pathway is activated upon ligand binding of cell surface death receptors such as tumor necrosis factor-a (TNF-a), initiating ligand-induced receptor trimerization and the formation of death-inducing signaling complex (DISC).…”

Section: Introductionmentioning

confidence: 99%

Antiandrogen-induced cell death in LNCaP human prostate cancer cells

et al. 2003

View full text Add to dashboard Cite

Antiandrogens such as Casodex (Bicalutamide) are designed to treat advance stage prostate cancer by interfering with androgen receptor-mediated cell survival and by initiating cell death. Treatment of androgen sensitive, non-metastatic LNCaP human prostate cancer cells with 0-100 microM Casodex or 0-10 ng/ml TNF-alpha induces cell death in 20-60% of the cells by 48 h in a dose-dependent manner. In cells treated with TNF-alpha, this is accompanied by the loss of mitochondrial membrane potential (DeltaPsim) and cell adhesion. In contrast, cells treated with Casodex display loss of cell adhesion, but sustained mitochondrial dehydrogenase activity. Overexpression of Bcl-2 in LNCaP cells attenuates the induction of cell death by TNF-alpha but not Casodex, suggesting that mitochondria depolarization is not required for the induction of cell death by Casodex. While both TNF-alpha and Casodex-induced release of cytochrome c in LNCaP cell is predominantely associated with the translocation and cleavage of Bax, our data also suggest that Casodex induces cell death by acting on components downstream of decline of DeltaPsim and upstream of cytochrome c release. Furthermore, while induction of both caspase-3 and caspase-8 activities are observed in TNF-alpha and Casodex-treated cells, a novel cleavage product of procaspase-8 is seen in Casodex-treated cells. Taken together, these data support the hypothesis that Casodex induces cell death by a pathway that is independent of changes in DeltaPsim and Bcl-2 actions and results in an extended lag phase of cell survival that may promote the induction of an invasive phenotype after treatment.

show abstract

Systemic treatment of hormone refractory prostate cancer

Cited by 11 publications

References 0 publications

Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer

Micellar Delivery of Bicalutamide and Embelin for Treating Prostate Cancer

Emergence of metastatic hormone‐refractory disease in prostate cancer after anti‐androgen therapy

Antiandrogen-induced cell death in LNCaP human prostate cancer cells

Contact Info

Product

Resources

About