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Open AccessEditorial

Statins and Cancer: A Complex Relationship Worth Exploring

by Jacek Bil

Pharmaceuticals 2023, 16(11), 1570; https://doi.org/10.3390/ph16111570 - 7 Nov 2023

Cited by 1 | Viewed by 1161

Abstract

This Special Issue, entitled “Statins and Cancer”, aims to demonstrate recent and new advances and future trends in using statins in the field of oncology [...] Full article

(This article belongs to the Special Issue Statins Use and Cancer)

Research

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11 pages, 775 KiB

Open AccessArticle

Association between Statin Use and Survival in Cancer Patients with Brain Metastasis: Retrospective Analysis from the Chinese Population

by Yu Min, Zheran Liu, Zhigong Wei, Ruidan Li, Jing Jin, Yu Zhang and Xingchen Peng

Pharmaceuticals 2022, 15(12), 1474; https://doi.org/10.3390/ph15121474 - 26 Nov 2022

Cited by 1 | Viewed by 1751

Abstract

Brain metastasis predicts a worse clinical outcome in cancer patients. Emerging observational evidence suggests that statin use has a protective role in overall cancer prevention. Whether statin use could also be a supplementary treatment for advanced-stage cancers remains under researched and controversial. Data [...] Read more.

Brain metastasis predicts a worse clinical outcome in cancer patients. Emerging observational evidence suggests that statin use has a protective role in overall cancer prevention. Whether statin use could also be a supplementary treatment for advanced-stage cancers remains under researched and controversial. Data for cancer patients with brain metastasis were selected from the linked electronic medical care records of the West China Hospital between October 2010 and July 2019. Fisher’s exact chi-square test was used to compare the differences between cohorts. Multivariate Cox analysis was conducted to adjust the potential confounders in evaluating the role of statin use in the overall survival (OS) of cancer patients with brain metastasis. There were 4510 brain metastatic patients included in this retrospective study. The overall statin use rate in our patients was 5.28% (219 cases/4510 cases). Compared with the non-statin use cohort, patients who received statin therapy showed a decreased Karnofsky performance score (KPS, p < 0.001) and lower high-density lipoprotein (HDL, p = 0.020) but higher body mass index (BMI, p = 0.002) and triglyceride (TG, p < 0.001) at admission. There was no association between statin use and the OS of the cancer patients with brain metastasis (Hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.73–1.07, p = 0.213) during the univariate analysis. However, after adjusting for baseline patient characteristics, metabolism indicators, and cancer-specific factors, statin use was shown to have a significant protective role, aiding the survival of the cancer patients with brain metastasis (_adjustHR = 0.82, 95%CI: 0.69–0.99, p = 0.034). Our results highlight that statin use shows significant survival benefits in cancer patients with brain metastasis. However, future research is needed to validate our findings. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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14 pages, 3404 KiB

Open AccessArticle

Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models

by Chao-Yi Chen, Yi-Feng Yang, Paul C. Wang, Liang Shan, Stephen Lin, Po-Jung Chen, Yi-Jung Chen, Han-Sun Chiang, Jaw-Town Lin, Chi-Feng Hung and Yao-Jen Liang

Pharmaceuticals 2022, 15(11), 1408; https://doi.org/10.3390/ph15111408 - 14 Nov 2022

Cited by 2 | Viewed by 2044

Abstract

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This [...] Read more.

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This study used different pancreatic cancer cell lines and in different animal models to confirm the relationship between simvastatin and pancreatic cancer. Flow cytometry and luciferase-based bioluminescent images were used to investigate the cell cycle and tumor growth changes under simvastatin treatment. Simvastatin decreased the MIA PaCa-2 cells, PANC-1 cells, and BxPC-3 cell viability significantly and may arrest the cell cycle in the G0 phase. During in vivo study, subcutaneously implanted simvastatin pre-treated pancreatic cancer cells and intraperitoneally treated simvastatin continuously demonstrated a slower tumor growth rate and decreased the tumor/body weight ratio significantly. In intravenous implant models, implanted simvastatin-pre-treated BxPC-3 cells and cells treated along with simvastatin significantly decreased the tumor growth curve. Implanting the simvastatin-pre-treated pancreatic cells in the subcutaneous model showed better growth inhibition than the intravenous model. These results suggest simvastatin treatment may relate to different signaling pathways in local growth and metastasis. Pancreatic cancer cells presented different growth patterns in different animal-induced models, which could be important for clinical reference when it comes to the relationship of long-term statin use and pancreatic cancer. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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14 pages, 1376 KiB

Open AccessEditor’s ChoiceArticle

Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality

by Konrad Stepien, Karol Nowak, Natalia Kachnic, Grzegorz Horosin, Piotr Walczak, Aleksandra Karcinska, Tomasz Schwarz, Mariusz Wojtas, Magdalena Zalewska, Maksymilian Pastuszak, Bogdan Wegrzyn, Jadwiga Nessler and Jarosław Zalewski

Pharmaceuticals 2022, 15(8), 919; https://doi.org/10.3390/ph15080919 - 25 Jul 2022

Cited by 9 | Viewed by 2762

Abstract

Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients [...] Read more.

Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients were observed within a median follow-up of 69.2 (37.8–79.9) months. On discharge, statins were prescribed less frequently in MI patients with cancer as compared to the non-cancer MI population (79.9% vs. 91.4%, p < 0.001). The most common statin in both groups was atorvastatin. The long-term mortality was higher in MI patients not treated vs. those treated with statins, both in non-cancer (29.5%/year vs. 6.7%/year, p < 0.001) and cancer groups (53.9%/year vs. 24.9%/year, p < 0.05), respectively. Patient’s age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.03–1.05, p < 0.001, per year), an active cancer (HR 2.42, 95% CI 1.89–3.11, p < 0.001), hemoglobin level (HR 1.14, 95% CI 1.09–1.20, p < 0.001, per 1 g/dL decrease), and no statin on discharge (HR 2.13, 95% CI 1.61–2.78, p < 0.001) independently increased long-term mortality. In MI patients, simultaneous diagnosis of an active cancer was associated with less frequently prescribed statins on discharge. Irrespective of cancer diagnosis, no statin use was found as an independent predictor of increased long-term mortality. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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14 pages, 497 KiB

Open AccessArticle

Effects of the Prior Use of Statins on Head and Neck Cancer Risk: A Hospital-Based Case–Control Study

by Constanza Saka-Herrán, Enric Jané-Salas, Antonio Mano-Azul, Aina Torrejón-Moya, Albert Estrugo-Devesa and José López-López

Pharmaceuticals 2022, 15(5), 579; https://doi.org/10.3390/ph15050579 - 6 May 2022

Cited by 8 | Viewed by 1932

Abstract

Mechanisms related to the potential beneficial effects of statins on cancer are mainly related to the inhibition of the mevalonate pathway. The purpose of this study was to assess the association between prior use of statins and the risk of head and neck [...] Read more.

Mechanisms related to the potential beneficial effects of statins on cancer are mainly related to the inhibition of the mevalonate pathway. The purpose of this study was to assess the association between prior use of statins and the risk of head and neck cancer. A hospital-based case–control study was conducted at the Dentistry Hospital of the University of Barcelona, including 101 incident cases of head and neck cancer and 101 controls matched to cases by age and sex. Multivariate logistic regression models were used to assess the association between prior statin exposure and head and neck cancer risk. Of the 202 patients included in total, 28.2% had previously received prescriptions for statins. Prior use of statins was found in 25.7% of cases and 30.7% of controls. Exposure to statins was not associated with head and neck cancer risk (OR = 0.72; 95% CI 0.28–1.84; p = 0.49). There was also no time- or dose-dependent association. Similar trends were observed when analyzed by subsites of cancer and recurrence rate. Our findings do not support a beneficial effect of prior statin exposure on head and neck cancer risk. Future research relying on observational data should emulate randomized clinical trials before clinical implications for repurposing drugs can be drawn. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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18 pages, 4225 KiB

Open AccessArticle

Response Predictive Markers and Synergistic Agents for Drug Repositioning of Statins in Ovarian Cancer

by Yusuke Kobayashi, Takashi Takeda, Haruko Kunitomi, Fumiko Chiwaki, Masayuki Komatsu, Shimpei Nagai, Yuya Nogami, Kosuke Tsuji, Kenta Masuda, Hideaki Ogiwara, Hiroki Sasaki, Kouji Banno and Daisuke Aoki

Pharmaceuticals 2022, 15(2), 124; https://doi.org/10.3390/ph15020124 - 21 Jan 2022

Cited by 5 | Viewed by 4917

Abstract

In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve [...] Read more.

In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve clinical application. In the present study, we demonstrated that statins have a multifaceted mode of action in ovarian cancer and involve pathways other than protein prenylation. To identify biomarkers that predict the response to statins, we subjected ovarian cancer cells to microarray analysis and calculated Pearson’s correlation coefficients between gene expression and cell survival after statin treatment. The results showed that VDAC1 and LDLRAP1 were positively and negatively correlated with the response to statins, respectively. Histoculture drug response assays revealed that statins were effective in clinical samples. We also confirmed the synergistic effects of statins with paclitaxel and panobinostat and determined that statins are hematologically safe to administer to statin-treated mice. Future clinical trials based on the expression of the biomarkers identified in this study for repurposing statins for ovarian cancer treatment are warranted. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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17 pages, 3606 KiB

Open AccessArticle

Association between Statin Use and Gastric Cancer: A Nested Case-Control Study Using a National Health Screening Cohort in Korea

by Mi Jung Kwon, Ho Suk Kang, Joo-Hee Kim, Ji Hee Kim, Se Hoon Kim, Nan Young Kim, Eun Sook Nam, Kyueng-Whan Min and Hyo Geun Choi

Pharmaceuticals 2021, 14(12), 1283; https://doi.org/10.3390/ph14121283 - 8 Dec 2021

Cited by 15 | Viewed by 3136

Abstract

Concerns about the hazards of statins on the development and mortality of stomach cancers remain controversial. Here, we investigated the likelihood of incident gastric cancers and related mortality depending on statin exposure, statin type, and the duration of use. This nested case–control-designed study [...] Read more.

Concerns about the hazards of statins on the development and mortality of stomach cancers remain controversial. Here, we investigated the likelihood of incident gastric cancers and related mortality depending on statin exposure, statin type, and the duration of use. This nested case–control-designed study was composed of 8798 patients who were diagnosed with gastric cancer and matched with 35,192 controls at a 1:4 ratio based on propensity scores of age, sex, residential area, and income from the Korean National Health Insurance Service—Health Screening Cohort database (2002–2015). Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior use of statins (any statin, hydrophilic statins vs. lipophilic statins) with incident gastric cancer and its mortality depending on the medication duration (<180 days, 180–545 days, and >545 days) after adjusting for multiple covariates. After adjustment, the use of any statin, hydrophilic statins, or lipophilic statins showed significant associations with lower odds for incident stomach cancer when used for a short-term period (180–545 days) (OR = 0.88, 95% CI = 0.81–0.86, p = 0.002; OR = 0.78, 95% CI = 0.66–0.92, p = 0.004; and OR = 0.91, 95% CI = 0.84–0.99, p = 0.039, respectively) compared to the control group. Hydrophilic statin use for 180–545 days was associated with 53% lower overall mortality (OR = 0.47; 95% CI = 0.29–0.77). In subgroup analyses, beneficial effects on both cancer development and mortality persisted in patients ≥65 years old, patients with normal blood pressure, and patients with high fasting glucose levels. There were no such associations with long-term statin use (>545 days). Thus, the current nationwide cohort study suggests that prior short-term statin use may have anti-gastric cancer benefits in elderly patients with hyperglycemia. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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9 pages, 992 KiB

Open AccessArticle

Sex-Differences in Discontinuation of Statin Treatment in Cancer Patients the Year before Death

by Gabriella Frisk, Helena Bergström, Maria Helde Frankling and Linda Björkhem-Bergman

Pharmaceuticals 2021, 14(4), 368; https://doi.org/10.3390/ph14040368 - 16 Apr 2021

Cited by 4 | Viewed by 2358

Abstract

Statin treatment is often terminated in patients with advanced cancer but guidelines for statin discontinuation are still lacking. The aim of this study was to investigate sex-differences in time-points of statin discontinuation in patients with advanced cancer. Medical records from 1535 deceased patients [...] Read more.

Statin treatment is often terminated in patients with advanced cancer but guidelines for statin discontinuation are still lacking. The aim of this study was to investigate sex-differences in time-points of statin discontinuation in patients with advanced cancer. Medical records from 1535 deceased patients enrolled at a Palliative Home Care Unit were reviewed. A total of 149 patients (42 women and 107 men) who were diagnosed with cancer, and were treated with statins one year before death, were identified. Statin treatment was terminated earlier in women than in men, 3.0 months prior to death (IQR 0.88–7.25) as compared to 1.5 months (IQR 0.5–4.0) (p < 0.05), respectively. In a longitudinal analysis there was a significant difference between men and women still on statin treatment at all studied time-points, 9, 6, and 3 months before death (p < 0.05), where women terminated statin treatment earlier in the disease trajectory. Baseline demographics were similar between the sexes except that more men than women had a history of previous cardiovascular events (p < 0.01). However, neither the indication for statin treatment, i.e., primary prevention versus secondary prevention, nor age could explain the sex-difference in statin discontinuation. There was no difference in cardiovascular events or mortality between men and women after statin discontinuation. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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Review

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26 pages, 1766 KiB

Open AccessReview

The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action

by Yen My Vuu, Ashraf Kadar Shahib and Mojgan Rastegar

Pharmaceuticals 2023, 16(7), 914; https://doi.org/10.3390/ph16070914 - 22 Jun 2023

Cited by 7 | Viewed by 4851

Abstract

Statins are common drugs that are clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins are considered to be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity to facilitate its ability to cross the blood-brain barrier. [...] Read more.

Statins are common drugs that are clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins are considered to be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity to facilitate its ability to cross the blood-brain barrier. Recent studies have suggested that simvastatin could be a promising therapeutic option for different brain complications and diseases ranging from brain tumors (i.e., medulloblastoma and glioblastoma) to neurological disorders (i.e., Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). Specific mechanisms of disease amelioration, however, are still unclear. Independent studies suggest that simvastatin may reduce the risk of developing certain neurodegenerative disorders. Meanwhile, other studies point towards inducing cell death in brain tumor cell lines. In this review, we outline the potential therapeutic effects of simvastatin on brain complications and review the clinically relevant molecular mechanisms in different cases. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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27 pages, 1325 KiB

Open AccessReview

Novel Effects of Statins on Cancer via Autophagy

by Daniela Mengual, Luz Elena Medrano, Wendy Villamizar-Villamizar, Estefanie Osorio-Llanes, Evelyn Mendoza-Torres and Samir Bolívar

Pharmaceuticals 2022, 15(6), 648; https://doi.org/10.3390/ph15060648 - 24 May 2022

Cited by 9 | Viewed by 4276

Abstract

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The [...] Read more.

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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27 pages, 1766 KiB

Open AccessReview

Effect of Statins on Lung Cancer Molecular Pathways: A Possible Therapeutic Role

by Gianmarco Marcianò, Caterina Palleria, Alessandro Casarella, Vincenzo Rania, Emanuele Basile, Luca Catarisano, Cristina Vocca, Luigi Bianco, Corrado Pelaia, Erika Cione, Bruno D’Agostino, Rita Citraro, Giovambattista De Sarro and Luca Gallelli

Pharmaceuticals 2022, 15(5), 589; https://doi.org/10.3390/ph15050589 - 10 May 2022

Cited by 16 | Viewed by 3330

Abstract

Lung cancer is a common neoplasm, usually treated through chemotherapy, radiotherapy and/or surgery. Both clinical and experimental studies on cancer cells suggest that some drugs (e.g., statins) have the potential to improve the prognosis of cancer. In fact, statins blocking the enzyme “hydroxy-3-methylglutaryl-coenzyme [...] Read more.

Lung cancer is a common neoplasm, usually treated through chemotherapy, radiotherapy and/or surgery. Both clinical and experimental studies on cancer cells suggest that some drugs (e.g., statins) have the potential to improve the prognosis of cancer. In fact, statins blocking the enzyme “hydroxy-3-methylglutaryl-coenzyme A reductase” exert pleiotropic effects on different genes involved in the pathogenesis of lung cancer. In this narrative review, we presented the experimental and clinical studies that evaluated the effects of statins on lung cancer and described data on the effectiveness and safety of these compounds. We also evaluated gender differences in the treatment of lung cancer to understand the possibility of personalized therapy based on the modulation of the mevalonate pathway. In conclusion, according to the literature data, statins exert multiple effects on lung cancer cells, even if the evidence for their use in clinical practice is lacking. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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26 pages, 1863 KiB

Open AccessReview

Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

by Yoichi Morofuji, Shinsuke Nakagawa, Kenta Ujifuku, Takashi Fujimoto, Kaishi Otsuka, Masami Niwa and Keisuke Tsutsumi

Pharmaceuticals 2022, 15(2), 151; https://doi.org/10.3390/ph15020151 - 26 Jan 2022

Cited by 46 | Viewed by 10835

Abstract

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial [...] Read more.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering’. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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13 pages, 1647 KiB

Open AccessEditor’s ChoiceReview

The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis

by Yu-Chen Hou and Yu-Hsuan Shao

Pharmaceuticals 2022, 15(2), 131; https://doi.org/10.3390/ph15020131 - 22 Jan 2022

Cited by 7 | Viewed by 3206

Abstract

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause [...] Read more.

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64–0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49–0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66–1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62–1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39–1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68–0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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15 pages, 701 KiB

Open AccessReview

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

by Beniamin Oskar Grabarek, Dariusz Boroń, Emilia Morawiec, Piotr Michalski, Veronica Palazzo-Michalska, Łukasz Pach, Barbara Dziuk, Magdalena Świder and Nikola Zmarzły

Pharmaceuticals 2021, 14(12), 1220; https://doi.org/10.3390/ph14121220 - 25 Nov 2021

Cited by 16 | Viewed by 3783

Abstract

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used [...] Read more.

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used statins are simvastatin, rosuvastatin and atorvastatin. The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity. Statins are also involved in the regulation of the histone acetylation level, the disturbance of which can lead to abnormal activity of genes involved in the regulation of proliferation, differentiation and apoptosis. As a result, tumor growth and its invasion may be promoted, which is associated with a poor prognosis. High levels of histone deacetylases are observed in many cancers; therefore, one of the therapeutic strategies is to use their inhibitors. Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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25 pages, 2156 KiB

Open AccessReview

Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance

by Nirmala Tilija Pun and Chul-Ho Jeong

Pharmaceuticals 2021, 14(5), 470; https://doi.org/10.3390/ph14050470 - 16 May 2021

Cited by 36 | Viewed by 6905

Abstract

Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., [...] Read more.

Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., the use of old drugs for new therapeutic indications), which is an economical, safe, and efficacious approach as it is emerged from clinical drug development or may even be marketed with a well-established safety profile and optimal dosing. Statins are inhibitors of HMG-CoA reductase in cholesterol biosynthesis and are used in the treatment of hypercholesterolemia, atherosclerosis, and obesity. As cholesterol is linked to the initiation and progression of cancer, statins have been extensively used in cancer therapy with a concept of drug repurposing. Many studies including in vitro and in vivo have shown that statin has been used as monotherapy to inhibit cancer cell proliferation and induce apoptosis. Moreover, it has been used as a combination therapy to mediate synergistic action to overcome anti-cancer drug resistance as well. In this review, the recent explorations are done in vitro, in vivo, and clinical trials to address the action of statin either single or in combination with anti-cancer drugs to improve the chemotherapy of the cancers were discussed. Here, we discussed the emergence of statin as a lipid-lowering drug; its use to inhibit cancer cell proliferation and induction of apoptosis as a monotherapy; and its use in combination with anti-cancer drugs for its synergistic action to overcome anti-cancer drug resistance. Furthermore, we discuss the clinical trials of statins and the current possibilities and limitations of preclinical and clinical investigations. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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13 pages, 1538 KiB

Open AccessReview

Statins: HMG-CoA Reductase Inhibitors as Potential Anticancer Agents against Malignant Neoplasms in Women

by Anna Markowska, Michał Antoszczak, Janina Markowska and Adam Huczyński

Pharmaceuticals 2020, 13(12), 422; https://doi.org/10.3390/ph13120422 - 25 Nov 2020

Cited by 18 | Viewed by 5438

Abstract

Statins, also known as HMG-CoA inhibitors, are a class of bioactive small molecules that efficiently reduce the levels of cholesterol, and therefore are commonly used to manage and prevent various cardiovascular diseases. With respect to their original medical indications, statins are currently in [...] Read more.

Statins, also known as HMG-CoA inhibitors, are a class of bioactive small molecules that efficiently reduce the levels of cholesterol, and therefore are commonly used to manage and prevent various cardiovascular diseases. With respect to their original medical indications, statins are currently in the group of the most prescribed drugs worldwide. Of note is that statins are perceived actually rather as agents that have pleiotropic activities; in addition to their inhibitory activity on the production of endogenous cholesterol. Statins may also affect cell proliferation, angiogenesis and/or migration (metastasis) of different cancer cells, and play a positive role in the chemoprevention of cancer, thus being the excellent candidates to be repurposed in oncology. Particularly intriguing in this context seems to be the promising role of statins on both the incidence and course of common malignant neoplasms in women. In this article, we review and discuss the effect of the use of statins in the treatment of three types of cancer, i.e., breast, endometrial and ovarian cancer, with the highest mortality among gynecological cancers. Full article

(This article belongs to the Special Issue Statins Use and Cancer)

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