The role of metformin, statins and diet in men on active surveillance for prostate cancer

Tiwari, Raj; Fleshner, Neil

doi:10.1007/s00345-021-03858-4

Cited by 5 publications

(5 citation statements)

References 56 publications

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“…Until recently, no RCT have been done to ascertain the effect of metformin in low risk PCa. 95 However, given the promising data seen in preclinical and clinical studies in the last decade, the Metformin Active Surveillance Trial (MAST) has been set up to evaluate the role of metformin in reducing progression amongst men on expectant management for low risk PCa. This is a phase III randomized, double-blinded, placebo-controlled trial that is ongoing and estimated to be completed by 2024.…”

Section: Discussionmentioning

confidence: 99%

“…Five meta‐analyses conclusively indicated that metformin reduced biochemical recurrence (BCR) of PCa, 28,35–38 highlighting the possibility of repurposing this antidiabetic drug as an antitumour agent in PCa of various stages (Table 2). Until recently, no RCT have been done to ascertain the effect of metformin in low risk PCa 95 . However, given the promising data seen in preclinical and clinical studies in the last decade, the Metformin Active Surveillance Trial (MAST) has been set up to evaluate the role of metformin in reducing progression amongst men on expectant management for low risk PCa.…”

Section: Discussionmentioning

confidence: 99%

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Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models

et al. 2022

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Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta‐analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta‐analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta‐analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models

et al. 2022

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“…Several epidemiological studies have shown that diabetic patients treated with Met have a lower risk of developing cancers [ 106 ]. There are therefore many clinical trials that have used Met as an adjuvant in the treatment of many types of cancer [ 107 , 108 ]. From the point of view of the molecular mechanism, Met can affect a large number of molecules and cellular signalings such as influencing gluconeogenesis, metabolic pathways, and mitochondrial cellular respiration [ 109 ].…”

Section: Tumor Prevention and Treatmentsmentioning

confidence: 99%

Li–Fraumeni Syndrome: Mutation of TP53 Is a Biomarker of Hereditary Predisposition to Tumor: New Insights and Advances in the Treatment

Rocca

Blandino

D’Antona

et al. 2022

Cancers

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Li–Fraumeni syndrome (LFS) is a rare familial tumor predisposition syndrome with autosomal dominant inheritance, involving germline mutations of the TP53 tumor suppressor gene. The most frequent tumors that arise in patients under the age of 45 are osteosarcomas, soft-tissue sarcomas, breast tumors in young women, leukemias/lymphomas, brain tumors, and tumors of the adrenal cortex. To date, no other gene mutations have been associated with LFS. The diagnosis is usually confirmed by genetic testing for the identification of TP53 mutations; therefore, these mutations are considered the biomarkers associated with the tumor spectrum of LFS. Here, we aim to review novel molecular mechanisms involved in the oncogenic functions of mutant p53 in LFS and to discuss recent new diagnostic and therapeutic approaches exploiting TP53 mutations as biomarkers and druggable targets.

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“…Selenium, Vitamin E, and Soy). A literature review had shown overall mixed results [14] with some being stopped for cardiovascular toxicity (Refocoxib) [15], increased prostate cancer risk (Vitamin E) [16] and most famously two trials that showed a decreased risk of prostate cancer overall but increased high-grade disease in the treatment arm (PCPT and REDUCE trials) [17,18].…”

Section: Role Of Primary Prevention Strategies In High-risk Carriersmentioning

confidence: 99%

The role of prophylactic prostatectomy as a primary prevention strategy in high-risk germline mutation carriers

Tiwari

Clark

Fleshner

2022

Current Opinion in Urology

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Purpose of reviewMen with high-risk germline mutations are at significantly higher risk of developing and dying from prostate cancer. Current screening and treatment paradigms may lead to missed opportunities for cure. Herein we review the current literature on prevention, screening and treatment of these carriers and explore the potential role of prophylactic prostatectomy in primary prevention of prostate cancer mortality.Recent findingsProstate-specific antigen (PSA)-based screening has demonstrated marginal benefits in prostate cancer (PCa) survival and uncertainty remains on its true benefit among high-risk carriers. Recent results indicate that PCa in BRCA 2 carriers occurs at a higher incidence, younger age and progresses more rapidly compared with noncarriers. An intensified screening protocol of MRI and PSA in young carriers demonstrated how using PSA values alone may be insufficient. Current evidence indicates that high-risk carriers have worse survival outcomes after undergoing radical treatment for screening detected disease when compared with noncarriers.SummaryProphylactic prostatectomy within the context of a clinical trial is a reasonable primary prevention option for discussion with high-risk carriers, especially BRCA2 carriers during the shared decision-making process. Limitations exist in the current strategies of early PSA screening followed by radical treatment in this group.

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The role of metformin, statins and diet in men on active surveillance for prostate cancer

Cited by 5 publications

References 56 publications

Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models

Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models

Li–Fraumeni Syndrome: Mutation of TP53 Is a Biomarker of Hereditary Predisposition to Tumor: New Insights and Advances in the Treatment

The role of prophylactic prostatectomy as a primary prevention strategy in high-risk germline mutation carriers

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