Identification of Candidate Biomarkers of Therapeutic Response to Docetaxel by Proteomic Profiling

Zhao, Liangli; Lee, Brian Y.; Brown, David A.; Molloy, Mark P.; Marx, Gavin; Pavlakis, Nick; Boyer, Michael; Stockler, Martin R.; Kaplan, Warren; Breit, Samuel N.; Sutherland, Robert L.; Henshall, Susan M.; Horvath, Lisa G.

doi:10.1158/0008-5472.can-08-4901

Cited by 95 publications

(118 citation statements)

References 34 publications

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“…Moreover, a similar trend has been observed in the serum/plasma of patients with Docetaxel-resistant PCa with a clear impact on patients' survival. 92 This correlates well with previously published data; 93 however, in vitro data showed a direct link between GDF-15 and Docetaxel resistance. Androgen independent PCa PC3 cells treated with GDF-15 became partially resistant to Docetaxel and Docetaxel-resistant PC3 cells treated with GDF-15 shRNA showed restored susceptibility to Docetaxel.…”

Section: Gdf-15 In Pcasupporting

confidence: 91%

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Vaňhara

Hampl

Kozubı́k

et al. 2012

Prostate Cancer Prostatic Dis

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Deregulation of expression and function of cytokines belonging to the transforming growth factor-b (TGF-b) family is often associated with various pathologies. For example, this cytokine family has been considered a promising target for cancer therapy. However, the detailed functions of several cytokines from the TGF-b family that could have a role in cancer progression and therapy remain unclear. One of these molecules is growth/differentiation factor-15 (GDF-15), a divergent member of the TGF-b family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with cancer progression, including prostate cancer (PCa). However, studies clearly demonstrating the mechanisms for signal transduction and functions in cell interaction, cancer progression and therapy are still lacking. New GDF-15 roles have recently been identified for modulating osteoclast differentiation and for therapy for PCa bone metastases. Moreover, GDF-15 is as an abundant cytokine in seminal plasma with immunosuppressive properties. We discuss studies that focus on the regulation of GDF-15 expression and its role in tissue homeostasis, repair and the immune response with an emphasis on the role in PCa development.

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Section: Gdf-15 In Pcasupporting

confidence: 91%

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Vaňhara

Hampl

Kozubı́k

et al. 2012

Prostate Cancer Prostatic Dis

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“…Docetaxel-resistant sublines (PC3-Rx and DU145-Rx) were established and maintained as previously described (18). All cell lines were used within 10 passages and for less than 3 months after reviving from frozen storage, routinely tested to confirm chemosensitivity by cell viability assay, and independently authenticated by Cell Bank Australia in May 2013 using a short tandem repeat profiling approach.…”

Section: Cell Cultures and Cell Linesmentioning

confidence: 99%

“…This was based on Trypan blue exclusion (18). The concentration of drug required to kill 50% of the cells (IC 50 ) was calculated, as previously described (18).…”

Section: Cell Viability Assaymentioning

confidence: 99%

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Phosphoproteomic Profiling Identifies Focal Adhesion Kinase as a Mediator of Docetaxel Resistance in Castrate-Resistant Prostate Cancer

Lee

Hochgräfe

Lin

et al. 2014

Molecular Cancer Therapeutics

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Docetaxel remains the standard-of-care for men diagnosed with metastatic castrate-resistant prostate cancer (CRPC). However, only approximately 50% of patients benefit from treatment and all develop docetaxelresistant disease. Here, we characterize global perturbations in tyrosine kinase signaling associated with docetaxel resistance and thereby develop a potential therapeutic strategy to reverse this phenotype. Using quantitative mass spectrometry-based phosphoproteomics, we identified that metastatic docetaxel-resistant prostate cancer cell lines (DU145-Rx and PC3-Rx) exhibit increased phosphorylation of focal adhesion kinase (FAK) on Y397 and Y576, in comparison with parental controls (DU145 and PC3, respectively). Bioinformatic analyses identified perturbations in pathways regulating focal adhesions and the actin cytoskeleton and in protein-protein interaction networks related to these pathways in docetaxel-resistant cells. Treatment with the FAK tyrosine kinase inhibitor (TKI) PF-00562271 reduced FAK phosphorylation in the resistant cells, but did not affect cell viability or Akt phosphorylation. Docetaxel administration reduced FAK and Akt phosphorylation, whereas cotreatment with PF-00562271 and docetaxel resulted in an additive attenuation of FAK and Akt phosphorylation and overcame the chemoresistant phenotype. The enhanced efficacy of cotreatment was due to increased autophagic cell death, rather than apoptosis. These data strongly support that enhanced FAK activation mediates chemoresistance in CRPC, and identify a potential clinical niche for FAK TKIs, where coadministration with docetaxel may be used in patients with CRPC to overcome chemoresistance. Mol Cancer Ther; 13(1); 190-201. Ó2013 AACR.

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“…High serum concentrations of MIC-1 have been observed in patients with pancreatic (Koopmann et al, 2004(Koopmann et al, , 2006, gastric (Baek et al, 2009), and breast cancer (Welsh et al, 2003), and have been associated with adverse survival in colorectal cancer and glioblastoma (Shnaper et al, 2009). In prostate cancer, high patient serum levels of MIC-1 have been associated with increased disease stage (Selander et al, 2007), docetaxel resistance (Zhao et al, 2009), and adverse survival . In prostate cancer bone metastases, MIC-1 induced osteoclast activation (Wakchoure et al, 2009).…”

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confidence: 99%

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

et al. 2010

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BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of X10 mg l -1 or modified Glasgow prognostic score (mGPS) of X1), and nutritional status were assessed in newly diagnosed OGC patients (n ¼ 293). Healthy volunteers (n ¼ 35) served as controls. RESULTS: MIC-1 was elevated in patients (median ¼ 1371 pg ml -1 ; range 141 -39 053) when compared with controls (median ¼ 377 pg ml -1 ; range 141 -3786; Po0.001). Patients with gastric tumours (median ¼ 1592 pg ml -1 ; range 141 -12 643) showed higher MIC-1 concentrations than patients with junctional (median ¼ 1337 pg ml -1 ; range 383 -39 053) and oesophageal tumours (median ¼ 1180 pg ml -1 ; range 258 -31 184; P ¼ 0.015). Patients showed a median weight loss of 6.4% (range 0.0 -33.4%), and 42% of patients had an mGPS of X1 or plasma CRP of X10 mg l -1 (median ¼ 9 mg l -1 ; range 1 -200). MIC-1 correlated positively with disease stage (r 2 ¼ 0.217; Po0.001), age (r 2 ¼ 0.332; Po0.001), CRP (r 2 ¼ 0.314; Po0.001), and mGPS (r 2 ¼ 0.336; Po0.001), and negatively with Karnofsky Performance Score (r 2 ¼ À0.269; Po0.001). However, although MIC-1 correlated weakly with dietary intake (r 2 ¼ 0.157; P ¼ 0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median ¼ 204 days; 95% CI 157 -251) when compared with patients with MIC-1 levels in the lower three quartiles (median ¼ 316 days; 95% CI 259 -373; P ¼ 0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

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Identification of Candidate Biomarkers of Therapeutic Response to Docetaxel by Proteomic Profiling

Cited by 95 publications

References 34 publications

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Phosphoproteomic Profiling Identifies Focal Adhesion Kinase as a Mediator of Docetaxel Resistance in Castrate-Resistant Prostate Cancer

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

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