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Growing evidence suggests that men prescribed a statin for cholesterol control have a lower risk of advanced prostate cancer (PCa) and improved treatment outcomes; however, the mechanism by which statins elicit their anti-neoplastic effects is not well understood and is likely multifaceted. Statins are potent and specific inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) metabolic pathway. This two-part series is a review of the observational and experimental data on statins as anti-cancer agents in PCa. In this article, we describe the functional role that deregulated MVA metabolism plays in PCa progression and summarize the biological evidence and rationale for targeting the MVA pathway, with statins and other agents, for the treatment of PCa., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the mevalonate pathway for growth and survival, and, therefore, are vulnerable to statin therapy. However, these immediately available, well-tolerated, and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care. In this review, we highlight recent advances and outline important considerations for advancing statins to clinical trials in oncology., (©2020 American Association for Cancer Research.)

Carpodesmia tamariscifolia is a brown alga rich in (poly)phenols with important cytotoxic and antioxidant effects. However, the relationship between its chemical composition and its effects is unknown. The aim of this study is to identify the potential compounds and mechanisms responsible for its main effects. The alga was extracted consecutively with hexane, dichloromethane and methanol and further fractionated using Sephadex LH-20 and silica gel columns when appropriate. The fractions were subjected to thin-layer chromatography and liquid chromatography-mass spectrometry analysis and evaluated for their total phenolic content (Folin-Ciocalteu assay), radical scavenging activity (DPPH assay), cytotoxic activity (MTT assay on the SH-SY5Y cell line), and ability to generate H 2 O 2 (Amplex Red assay). Chromatographic and phenolic analyses of the fractions indicate that abundant redox-active phenols are present in all the fractions and that a high amount of prenylated hydroquinone derivatives is present in the apolar ones. In the hexane and dichloromethane fractions, the cytotoxic and antioxidant activities are closely related to their phenolic content, whereas in the methanol fractions, the cytotoxicity is negatively related to the phenolic content and the antioxidant activity is positively related to it. In the same tests, hydroquinone behaves as both strong cytotoxic and antioxidant agent. H 2 O 2 assay shows that C. tamariscifolia fractions and hydroquinone can autoxidize and generate H 2 O 2 . Our results suggest that redox-active phenols produce the pharmacological effects described for C. tamariscifolia and that the hydroquinone moiety of prenylated hydroquinone derivatives is responsible for both cytotoxic (through a pro-oxidant mechanism secondary to its autoxidation) and antioxidant effects of the apolar fractions., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: The statin family of cholesterol-lowering drugs has been shown to induce tumor-specific apoptosis by inhibiting the rate-limiting enzyme of the mevalonate (MVA) pathway, HMG-CoA reductase (HMGCR). Accumulating evidence suggests that statin use may delay prostate cancer (PCa) progression in a subset of patients; however, the determinants of statin drug sensitivity in PCa remain unclear. Our goal was to identify molecular features of statin-sensitive PCa and opportunities to potentiate statin-induced PCa cell death., Methods: Deregulation of HMGCR expression in PCa was evaluated by immunohistochemistry. The response of PCa cell lines to fluvastatin-mediated HMGCR inhibition was assessed using cell viability and apoptosis assays. Activation of the sterol-regulated feedback loop of the MVA pathway, which was hypothesized to modulate statin sensitivity in PCa, was also evaluated. Inhibition of this statin-induced feedback loop was performed using RNA interference or small molecule inhibitors. The achievable levels of fluvastatin in mouse prostate tissue were measured using liquid chromatography-mass spectrometry., Results: High HMGCR expression in PCa was associated with poor prognosis; however, not all PCa cell lines underwent apoptosis in response to treatment with physiologically-achievable concentrations of fluvastatin. Rather, most cell lines initiated a feedback response mediated by sterol regulatory element-binding protein 2 (SREBP2), which led to the further upregulation of HMGCR and other lipid metabolism genes. Overcoming this feedback mechanism by knocking down or inhibiting SREBP2 potentiated fluvastatin-induced PCa cell death. Notably, we demonstrated that this feedback loop is pharmacologically-actionable, as the drug dipyridamole can be used to block fluvastatin-induced SREBP activation and augment apoptosis in statin-insensitive PCa cells., Conclusion: Our study implicates statin-induced SREBP2 activation as a PCa vulnerability that can be exploited for therapeutic purposes using clinically-approved agents., (Copyright © 2019 University Health Network. Published by Elsevier GmbH.. All rights reserved.)

Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances), liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

With intraarterial infusion, high levels of chemotherapeutic agents can be achieved in the tumoral area. We present our experience with open-ended guidewire (OEGW) associated with steerable guidewires (SGW) as superselective catheters for intraarterial chemotherapeutic infusion and embolization. This technique was used successfully in 62 patients (190 procedures) over 15 months.