Chemotherapy for patients with hormone-refractory prostate cancer

Joly, Fabien; Tannock, Ian F.

doi:10.1093/annonc/mdh445

Cited by 16 publications

(7 citation statements)

References 19 publications

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“…However, tumours will eventually progress to an androgen‐independent stage with poor prognosis. Different molecular mechanisms are responsible for the acquisition of this hormone‐refractory phenotype, including continuous activations of the androgen receptor axis , characterized also by a limited response to chemotherapy and radiotherapy . Thus, effective alternative therapeutic approaches for the treatment of prostate cancer are required.…”

Section: Introductionmentioning

confidence: 99%

Long pentraxin‐3 as an epithelial–stromal fibroblast growth factor‐targeting inhibitor in prostate cancer

Ronca

Alessi

Coltrini

et al. 2013

The Journal of Pathology

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Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up-regulates FGF2 and FGF8b production in murine TRAMP-C2 prostate cancer cells, activating a FGF-dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin-3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N-terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3-derived pentapeptide Ac-ARPCA-NH2 abolish the mitogenic response of murine TRAMP-C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT-activated TRAMP-C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP-C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP-C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP-C2 cells overexpress only the FGF-binding N-terminal PTX3 domain. In keeping with the anti-tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high-grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti-angiogenic and anti-neoplastic activity in prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Long pentraxin‐3 as an epithelial–stromal fibroblast growth factor‐targeting inhibitor in prostate cancer

Ronca

Alessi

Coltrini

et al. 2013

The Journal of Pathology

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“…At the present time, there is no effective cure for the advanced disease and androgen deprivation therapy (ADT) remains the principal treatment option (Feldman and Feldman, 2001). Unfortunately, most PCa patients treated with ADT eventually acquire castration-resistant phenotype, a form, which is highly aggressive and unresponsive to other therapies (Joly and Tannock, 2004; Sridhar et al , 2013). Therefore, characterisation of molecular targets facilitating PCa progression and metastasis, and deciphering their mechanisms of action is critically important to develop effective treatment approaches.…”

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confidence: 99%

Restoration of PPP2CA expression reverses epithelial-to-mesenchymal transition and suppresses prostate tumour growth and metastasis in an orthotopic mouse model

et al. 2014

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Background:Emergence of castration-resistance in prostate cancer (PCa) is invariably associated with aggressive and metastatic disease. Previously, we reported promotion of castration-resistance upon downregulation of PPP2CA (encoding catalytic subunit of protein phosphatase 2A (PP2A), α-isoform); however, its role in PCa growth and metastasis remained undetermined.Methods:PPP2CA was overexpressed/silenced in PCa cells by stable transfection. Gene expression was examined by reverse transcription polymerase chain reaction, immunoblot and immunofluorescence analyses, and transcriptional activity measured by luciferase-based promoter-reporter assay. Effect on PCa phenotype was studied in vitro and in orthotopic mouse model, and immunohistochemical/histological analyses performed to assess proliferation/apoptosis and confirm metastatic lesions.Results:An inverse association of PPP2CA expression was observed with epithelial-to-mesenchymal transition (EMT) and aggressive PCa phenotype. PPP2CA restoration resulted in decreased nuclear accumulation and transcriptional activity of β-catenin/NF-κB, and restitution of their activity abrogated PPP2CA-induced EMT reversal and suppression of PCa invasiveness. Akt mediated PPP2CA loss-induced nuclear accumulation of β-catenin/NF-κB through inactivation of Gsk3-β and IκB-α, respectively. Animal studies revealed a suppressive effect of PPP2CA expression on PCa growth and metastasis.Conclusions:Our findings suggest that PPP2CA downregulation serves as a molecular link between gain of castration-resistance and aggressive PCa phenotype, and its restoration could be an effective preventive/therapeutic approach against the advanced disease.

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“…Pendant de nombreuses anné es, ces patients recevaient un traitement hormonal initial puis des soins en confort quand la maladie devenait hormonoré fractaire. Dans les anné es 1990, la chimiothé rapie a é té introduite dans la prise en charge de ces malades é chappant à l'hormonothé rapie sur la base d'é tudes qui ont mis en é vidence une amé lioration des symptô mes douloureux et de la qualité de la vie en utilisant le questionnaire gé né -rique de l'EORTC [25]. Il s'agissait des premiè res é tudes qui privilé -giaient la qualité de la vie à la quantité de vie en prenant en compte le principal problè me qui est la douleur dans cette situation qui concerne principalement l'homme â gé [26].…”

Section: Abstract: Quality Of Life -Oncology -Elderlyunclassified