Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy

Mikkelsen, Marta Kramer; Thomsen, Frederik Birkebæk; Berg, Kasper Drimer; Jarden, Mary; Larsen, Signe Benzon; Hansen, Rikke Bølling; Brasso, Klaus

doi:10.1080/21681805.2017.1362032

Cited by 14 publications

(34 citation statements)

References 24 publications

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“…A total of 66 articles were excluded after the review of abstracts, and 35 studies were potentially eligible and evaluated in detail. Overall, nine studies with 101 773 patients were identified that were eligible for inclusion in the meta‐analysis . Specifically, three studies were related to abiraterone or enzalutamide, whereas the rest six articles were about ADT .…”

Section: Resultsmentioning

confidence: 99%

“…However, another meta‐analysis demonstrated that such a potentially beneficial effect of statins on PCa was only found in the patients receiving radiotherapy, but not in those who accepted radical prostatectomy . Intuitively, whether the effect of statins on PCa could vary along with treatment modality arouses increasing attention in clinical practice …”

Section: Introductionmentioning

confidence: 99%

“…Newer agents, including abiraterone and enzalutamide, have been approved to manage patients with metastatic castration‐resistant prostate cancer (mCRPC) . Although a handful of studies about the influence of statins on treatment outcomes in PCa patients who were treated with ADT or abiraterone/enzalutamide have been published, results are inconsistent and vary by studies. Considering that the combination of statins and ADT for PCa could possibly generate additional impacts on the overall treatment outcomes, investigations focusing on the most appropriate target patient population are of great clinical importance to optimize treatment responses and improve the quality of life in PCa patients.…”

Section: Introductionmentioning

confidence: 99%

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The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

Yang

Pang

et al. 2020

J Clin Pharm Ther

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What is known and objective: To evaluate the effects of statin use on the treatment outcomes (i.e. overall survival and cancer-specific survival) among advanced prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or abiraterone/enzalutamide. Methods: The original studies, examining the effects of statins on the outcomes (i.e. overall survival and cancer-specific survival) among PCa patients treated with ADT or abiraterone/enzalutamide, were identified through a systematic search by two independent reviewers in the PubMed, Cochrane, Embase, American Society of Clinical Oncology and European Society of Medical Oncology databases. Databases were searched using keywords (abiraterone OR enzalutamide OR androgen deprivation therapy) AND statin. In total, nine eligible studies from 111 references were included for final analysis.Results and discussion: Statin use significantly lowered the risk of all-cause mortality (100 709 patients, HR = 0.73, 95%CI = 0.64-0.83, P < .00001) and the risk of cancerspecific mortality (100 343 patients, HR = 0.64, 95% CI = 0.53-0.77, P < .00001) in advanced PCa patients treated with ADT. The sensitivity analysis showed that the results were reliable. However, it could not generate reliable evidence in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone/ enzalutamide, as relevant studies were limited and had inconsistent results.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

Yang

Pang

et al. 2020

J Clin Pharm Ther

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“…Certain mutations in the EGFR TK domain is one of the factors lead to the resistance to certain TKIs [14]. However, on the other hand, more and more studies showed that the genetic alterations are present in only a minority of patients who partially respond to treatment and are rare in tumors other than NSCLC [15, 26, 27]. Thus, the sensitivity of only a few tumors to EGFR TKIs can be explained by the presence of EGFR TK domain mutations.…”

Section: Discussionmentioning

confidence: 99%

The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells

Wang

Yang

Wang

et al. 2019

J Exp Clin Cancer Res

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Background/aims A novel paradigm in tumor biology suggests that osteosarcoma (OS) chemo-resistance is driven by osteosarcoma stem cell-like cells (OSCs). As the sensitivity of only a few tumors to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations, there is a need to elucidate mechanisms of resistance to EGFR-targeted therapies in OS that do not harbor TK sensitizing mutations to develop new strategies to circumvent resistance to EGFR inhibitors. Methods As a measure of the characters of OSCs, serum-free cultivation, cell viability test with erlotinib, and serial transplantation in vivo was used. Western blot assays were used to detect the association between erlotinib resistance and transforming growth factor beta (TGFβ)-induced epithelial-to-mesenchymal transition (EMT) progression. By using TaqMan qPCR miRNA array, online prediction software, luciferase reporter assays and western blot analysis, we further elucidated the mechanisms. Results Here, CD166 + cells are found in 10 out of 10 tumor samples. We characterize that CD166 + cells from primary OS tissues bear hallmarks of OSCs and erlotinib-resistance. TGFβ-induced EMT-associated kinase switch is demonstrated to promote erlotinib-resistance of CD166 + OSCs. Further mechanisms study show that TGFβ-induced EMT decreases miR-499a expression through the direct binding of Snail1/Zeb1 to miR-499a promoter. Overexpression of miR-499a in CD166 + OSCs inhibits TGFβ-induced erlotinib-resistance in vitro and in vivo. SHKBP1, the direct target of miR-499a, regulates EGFR activity reduction occurring concomitantly with a TGFβ-induced EMT-associated kinase switch to an AKT-activated EGFR-independent state. TGFβ-induced activation of AKT co-opts an increased SHKBP1 expression, which further regulates EGFR activity. In clinic, the ratio of the expression levels of SHKBP1 and miR-499a is highly correlated with EMT and resistance to erlotinib. Conclusion TGFβ–miR-499a–SHKBP1 network orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors in CD166 + OSCs, implies that inhibition of TGFβ induced EMT-associated kinase switch may reverse the chemo-resistance of OSCs to EGFR inhibitors. We also suggest that an elevated SHKBP1/miR-499a ratio is a molecular signature that characterizes the erlotinib-resistant OS, which may have clinical value as a predictive biomarker. Electronic supplementary material The online version of this article (10.1186/s13046-019-1195-y) contains supplementary material, which is available to authorized users.

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“…These studies suggest that statins may enhance the therapeutic effect of ADT. In contrast, one recent Danish study [20] failed to find any differences in progression-free survival or risk of progression between statin users and non-users in PCa patients primarily treated with ADT. Prostate cancer is known to be dependent on androgens and ADT is commonly used to manage advanced prostate 0.00 0.50 cancer.…”

Section: Discussionmentioning

confidence: 75%

Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study

Peltomaa¹,

Talala²,

Taari³

et al. 2019

European Urology Supplements

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Purpose Statins' cholesterol-lowering efficacy is well-known. Recent epidemiological studies have found that inhibition of cholesterol synthesis may have beneficial effects on prostate cancer (PCa) patients, especially patients treated with androgen deprivation therapy (ADT). We evaluated statins' effect on prostate cancer prognosis among patients treated with ADT. Materials and methods Our study population consisted of 8253 PCa patients detected among the study population of the Finnish randomized study of screening for prostate cancer. These were limited to 4428 men who initiated ADT during the follow-up. Cox proportional regression model adjusted for tumor clinical characteristics and comorbidities was used to estimate hazard ratios for risk of PSA relapse after ADT initiation and prostate cancer death. Results During the median follow-up of 6.3 years after the ADT initiation, there were 834 PCa deaths and 1565 PSA relapses in a study cohort. Statin use after ADT was associated with a decreased risk of PSA relapse (HR 0.73, 95% CI 0.65-0.82) and prostate cancer death (HR 0.82; 95% CI 0.69-0.96). In contrast, statin use defined with a one-year lag (HR 0.89, 95% CI 0.76-1.04), statin use before ADT initiation (HR 1.12, 95% CI 0.96-1.31), and use in the first year on ADT (HR 1.02, 95% CI 0.85-1.24) were not associated with prostate cancer death, without dose dependency. Conclusion Statin use after initiation of ADT, but not before, was associated with improved prostate cancer prognosis.

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Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy

Abstract: In the current study, statin use at time of PCa diagnosis was unrelated to time to progression in men primarily treated with ADT.

Cited by 14 publications

References 24 publications

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells

Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study

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