Anti-tumour activity of platinum compounds in advanced prostate cancer—a systematic literature review

Hager, Steven; Ackermann, Christoph; Joerger, Markus; Gillessen, Silke; Omlin, Aurelius

doi:10.1093/annonc/mdw156

Cited by 84 publications

(66 citation statements)

References 102 publications

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“…Carboplatin is a second-generation platinum agent that has fewer serious side effects than cisplatin. At present, none of the treatment regimens have demonstrated a significant overall survival benefit [38]. However, these platinum drugs are expected to be useful for a specific subtype of patients with HRPC, particularly in certain histological types such as neuroendocrine carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

et al. 2018

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Abstract:Patients with metastatic castration-resistant prostate cancer (mCRPC) have poor outcomes. Docetaxel (DTX)-based therapy is a current standard treatment for patients with mCRPC. Approaches combining conventional chemotherapeutic agents and nanoparticles (NPs), particularly iron oxide NPs, may overcome the serious side effects and drug resistance, resulting in the establishment of new therapeutic strategies. We previously reported the combined effects of

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Section: Discussionmentioning

confidence: 99%

Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

et al. 2018

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“…Platinum agents have been tested in many clinical trials of mCRPC with modest efficacy in unselected patients with adenocarcinoma alone or in combination, as observed across numerous single‐arm trials and even a phase 2 randomized clinical trial in combination with docetaxel after failure of docetaxel . Typically, response rates have ranged from 5% to 20%, including the phase 3 trial of oral satraplatin in unselected men with mCRPC .…”

Section: Selected Ongoing Clinical Trials Using Parp Inhibitors In Prmentioning

confidence: 99%

Exploiting DNA damage without repair: The activity of platinum chemotherapy in BRCA‐mutated prostate cancers

Humeniuk

Zhang

Armstrong

2017

Cancer

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“…While platinum agents are not routine for the treatment of mCRPC, there is an increasing use of these agents especially in those patients with a small-cell or neuroendocrine tumor variants [6]. In fact, some antitumor activity has been described for carboplatin, cisplatin, and satraplatin in mCRPC patients [10].…”

Section: Introductionmentioning

confidence: 99%

Taxane induces attenuation of the CXCR2/BCL-2 axis and sensitize prostate cancer to platinum-based treatments

Porras

Wang

Palomero

et al. 2020

Preprint

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BackgroundTaxanes are the most active chemotherapy agents in metastatic castration resistant prostate cancer (mCRPC) patients, yet resistance almost invariably occurs representing an important clinical challenge. Taxane-platinum combinations have shown clinical benefit in a subset of patients but the mechanistic basis and biomarkers remain elusive.ObjectiveTo identify mechanisms and response biomarkers for the antitumor efficacy of taxane-platinum combinations in mCRPC.Design, setting, and participantsTranscriptomic data from a publicly available mCRPC dataset of taxane-exposed and naïve patients was analysed to identify response biomarkers and emerging vulnerabilities. Functional and preclinical validation was performed in taxane resistant mCRPC cell lines and genetically engineered mouse models (GEMM).InterventionmCRPC cells were treated with docetaxel, cisplatin, carboplatin and the CXCR2 inhibitor, SB265610. Gain and loss of function in culture of CXCR2 was achieved by overexpression or siRNA-silencing. Preclinical assays in GEMM mice tested the anti-tumor efficacy of taxane-platinum combinations.Outcome measurements and statistical analysisProliferation, apoptosis and colony assays measured drug activity in vitro. Preclinical endpoints in mice included growth, survival and histopathology. Changes in CXCR2, BCL-2 and chemokines were analysed by RT-qPCR and Western Blot. Human expression data was analyzed using GSEA, hierarchical clustering and correlation studies. GraphPad Prism software, R-studio, were used for statistical and data analyses.Results and limitationsTranscriptomic data from taxane-exposed human mCRPC tumors correlates with a marked negative enrichment of apoptosis and inflammatory response pathways accompanied by a marked downregulation of CXCR2 and BCL-2. Mechanistically, we show that docetaxel treatment inhibits CXCR2 and that BCL-2 downregulation occurs as a downstream effect. Further, we demonstrated that taxane resistance is directly associated to CXCR2 expression and that targeting of CXCR2 sensitizes prostate cancer (PC) cells to cisplatin. Finally, taxane-platinum combinations in vivo are highly synergistic and previous exposure to taxanes sensitizes mCRPC tumors to second line cisplatin treatment.ConclusionsTogether our data identifies an acquired vulnerability in taxane treated mCRPC patients with potential predictive activity for platinum-based treatments.Patient summaryA subset of patients with aggressive and therapy resistant PC benefits from taxane-platinum combination chemotherapy however, we lack biomarkers and mechanistic basis about how that synergistic effect occurs. Here, using patient data and preclinical models, we found that taxanes reduce cancer cell scape mechanisms to chemotherapy-induced cell death, hence turning these cells more vulnerable to additional platinum treatment.

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Anti-tumour activity of platinum compounds in advanced prostate cancer—a systematic literature review

Cited by 84 publications

References 102 publications

Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

Exploiting DNA damage without repair: The activity of platinum chemotherapy in BRCA‐mutated prostate cancers

Taxane induces attenuation of the CXCR2/BCL-2 axis and sensitize prostate cancer to platinum-based treatments

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