Clinical Potential of Statins in Prostate Cancer Radiation Therapy

Hutchinson, Jack H.; Marignol, Laure

doi:10.21873/anticanres.11962

Cited by 12 publications

(12 citation statements)

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“…In combination with radiation, statins can improve clinical outcomes via their radiosensitizing properties. However, the available clinical data is conflicting ( 64 , 65 ). Here, upregulation of the Cholesterol Homeostasis gene set was associated with worse OS for CESC patients ( Figure 3H ; p= 0.012).…”

Section: Resultsmentioning

confidence: 99%

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Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

2021

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Although radiotherapy is given to more than 50% of cancer patients, little progress has been made in identifying optimal radiotherapy - drug combinations to improve treatment efficacy. Using molecular data from The Cancer Genome Atlas (TCGA), we extracted a total of 1016 cancer patients that received radiotherapy. The patients were diagnosed with head-and-neck (HNSC - 294 patients), cervical (CESC - 166 patients) and breast (BRCA - 549 patients) cancer. We analyzed mRNA expression patterns of 50 hallmark gene sets of the MSigDB collection, which we divided in eight categories based on a shared biological or functional process. Tumor samples were split into upregulated, neutral or downregulated mRNA expression for all gene sets using a gene set analysis (GSEA) pre-ranked analysis and assessed for their clinical relevance. We found a prognostic association between three of the eight gene set categories (Radiobiological, Metabolism and Proliferation) and overall survival in all three cancer types. Furthermore, multiple single associations were revealed in the other categories considered. To the best of our knowledge, our study is the first report suggesting clinical relevance of molecular characterization based on hallmark gene sets to refine radiation strategies.

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Section: Resultsmentioning

confidence: 99%

“…An interesting finding was the upregulation of the Cholesterol gene set associated with OS in CESC patients. The Cholesterol pathway has been successfully targeted with statins, however combinations with radiotherapy resulted in conflicting results ( 64 ), which should be further unravelled.…”

Section: Discussionmentioning

confidence: 99%

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

2021

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“…Our finding, the benefit of statin therapy particularly after diagnosis, is consistent with several large previous studies. With radio-sensitizing properties, statins have antitumor effects which support their beneficial use in prostate cancer 32. Raval et al33 performed a meta-analysis that included 34 observational cohort studies and found a 21% reduction in the risk of biochemical recurrence (BCR) in patients treated with statin and radiation therapy ( P =0.01).…”

Section: Discussionmentioning

confidence: 99%

<p>Statin and metformin therapy in prostate cancer patients with hyperlipidemia who underwent radiotherapy: a population-based cohort study</p>

Li¹,

Song²,

Qiu³

et al. 2019

CMAR

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PurposeTo evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan.Subjects and methodsNewly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000–2010. The survival rate was estimated by the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes.ResultsThe study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09–0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45–18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes.ConclusionThe finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

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“…Additionally, some studies have demonstrated a beneficial effect of statins in reducing PCa related mortality as well as overall PCa risk ( Katz et al, 2010 ; Marcella et al, 2012 ) whereas other studies have not revealed a significant effect ( Caon et al, 2014 ). Recently, conflicting data sourced from clinical outcomes obstruct the integration of neither beneficial nor harmful associations between the statin use and PCa ( Hutchinson and Marignol, 2017 ).…”

Section: Repurposed and Clinically Evaluated Non-cancer Drugs For Pcamentioning

confidence: 99%

Drug Repositioning for Effective Prostate Cancer Treatment

et al. 2018

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Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

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Clinical Potential of Statins in Prostate Cancer Radiation Therapy

Cited by 12 publications

References 50 publications

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures

<p>Statin and metformin therapy in prostate cancer patients with hyperlipidemia who underwent radiotherapy: a population-based cohort study</p>

Drug Repositioning for Effective Prostate Cancer Treatment

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