Statins as anti‐tumor agents: A paradigm for repurposed drugs

Cancer Reports, Journal Year: 2024, Volume and Issue: 7(5)

Published: May 1, 2024

Abstract Background Statins, frequently prescribed medications, work by inhibiting the rate‐limiting enzyme HMG‐CoA reductase (HMGCR) in mevalonate pathway to reduce cholesterol levels. Due their multifaceted benefits, statins are being adapted for use as cost‐efficient, safe and effective anti‐cancer treatments. Several studies have shown that specific types of cancer responsive statin medications since they rely on growth survival. Recent Findings Statin a class drugs known potent inhibition production typically treat high Nevertheless, there is growing interest repurposing treatment malignant neoplastic diseases, often conjunction with chemotherapy radiotherapy. The mechanism behind includes targeting apoptosis through BCL2 signaling pathway, regulating cell cycle via p53‐YAP axis, imparting epigenetic modulations altering methylation patterns CpG islands histone acetylation downregulating DNMTs HDACs respectively. Notably, some suggested potential chemo‐preventive effect, decreased occurrence tumor relapse enhanced survival rate were reported patients undergoing long‐term therapy. However, definitive endorsement usage therapy hinges population based clinical larger patient cohorts extended follow‐up periods. Conclusions properties seems reach beyond influence production. Further investigations necessary uncover effects promoting pathways. Given distinct attributes, might emerge promising contenders fight against tumorigenesis, appear enhance efficacy address limitations conventional

Language: Английский

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The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

The mechanical properties of the tumor microenvironment (TME) undergo significant changes during growth, primarily driven by alterations in extracellular (ECM) stiffness and viscoelasticity. These not only promote progression but also hinder therapeutic efficacy impairing drug delivery activating mechanotransduction pathways that regulate crucial cellular processes such as migration, proliferation, resistance to therapy. In this review, we examine mechanisms through which cells sense transmit signals maintain homeostasis biomechanically altered TME. We explore current computational modelling strategies for pathways, highlighting need developing models incorporate additional components mechanosignaling machinery. Furthermore, review available methods measuring tumors clinical settings aiming at restoring TME blocking deregulated pathways. Finally, propose proper characterization a deeper understanding landscape TME, both tissue levels, are essential account influence forces on treatment efficacy.

Language: Английский

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The Past and Future of Inflammation as a Target to Cancer Prevention

Cancer Prevention Research, Journal Year: 2024, Volume and Issue: 17(4), P. 141 - 155

Published: Jan. 25, 2024

Abstract Inflammation is an essential defense mechanism in which innate immune cells are coordinately activated on encounter of harmful stimuli, including pathogens, tissue injury, and toxic compounds metabolites to neutralize eliminate the instigator initiate healing regeneration. Properly terminated inflammation vital health, but uncontrolled runaway that becomes chronic begets a variety inflammatory metabolic diseases increases cancer risk. Making damaged tissues behave as “wounds do not heal” sustaining production growth factors whose physiologic function healing, accelerates emergence from premalignant lesions. In 1863, Rudolf Virchow, leading German pathologist, suggested possible association between tumor formation, it took another 140 years fully elucidate appreciate tumorigenic role inflammation. Key findings outlined molecular events cascade promote onset progression enabled better appreciation when where should be inhibited. These efforts triggered ongoing research work discover develop inflammation-reducing chemopreventive strategies for decreasing risk incidence.

Language: Английский

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Treatment of Epstein-Barr Virus infection in immunocompromised patients

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116270 - 116270

Published: May 10, 2024

Language: Английский

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Clinical significance of lipid pathway-targeted therapy in breast cancer

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Globally, breast cancer represents the most common and primary cause of death by in women. Lipids are crucial human physiology, serving as vital energy reserves, structural elements biological membranes, essential signaling molecules. The metabolic reprogramming lipid pathways has emerged a critical factor progression, drug resistance, patient prognosis. In this study, we delve into clinical implications pathway-targeted therapy cancer. We highlight key enzymes potential therapeutic targets involved metabolism reprogramming, their associations with progression treatment outcomes. Furthermore, detail trials exploring anticancer chemopreventive activity therapies targeting these However, efficacy remains controversial, highlighting urgent need for predictive biomarkers to identify subpopulations likely benefit from such treatment. propose Selective Lipid Metabolism Therapy Benefit Hypothesis, emphasizing importance personalized medicine optimizing patients.

Language: Английский

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Drug Repurposing and Nanotechnology for Topical Skin Cancer Treatment: Redirecting toward Targeted and Synergistic Antitumor Effects

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Skin cancer represents a major health concern due to its rising incidence and limited treatment options. Current treatments (surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy) often entail high costs, patient inconvenience, significant adverse effects, therapeutic efficacy. The search for novel options is also marked by the capital investment extensive development involved in drug discovery process. In response these challenges, repurposing existing drugs topical application optimizing their delivery through nanotechnology could be answer. This innovative strategy aims combine advantages of known pharmacological background commonly used expedite development, with nanosystem-based formulations, which among other allow improved skin permeation retention overall higher efficacy safety. present review provides critical analysis repurposed such as doxycycline, itraconazole, niclosamide, simvastatin, leflunomide, metformin, celecoxib, formulated into different nanosystems, namely, nanoemulsions nanoemulgels, nanodispersions, solid lipid nanoparticles, nanostructured carriers, polymeric hybrid lipid-polymer electrospun nanofibrous scaffolds, liposomes liposomal gels, ethosomes ethosomal aspasomes, outcomes battle against cancer. Enhanced antitumor effects on melanoma nonmelanoma research models are highlighted, some nanoparticles even showing intrinsic anticancer properties, leading synergistic effects. explored findings highly evidence potential approaches complement currently available strategies hope that might one day reach pharmaceutical market.

Language: Английский

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Carbohydrate kinase inhibition: a promising strategy in cancer treatment

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104308 - 104308

Published: Feb. 1, 2025

Language: Английский

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The Mevalonate Pathway in the Radiation Response of Cancer

International Journal of Radiation Oncology*Biology*Physics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Oncologic impact of statin use on patients treated with hepatectomy for intrahepatic cholangiocarcinoma

Hepatology Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 10, 2025

Abstract Aim Currently, the only recognized curative treatment for intrahepatic cholangiocarcinoma (ICC) is surgical resection. However, impact of various clinical factors, including patient history and pharmacological interventions, on survival outcomes still not fully understood. We aimed to bridge this knowledge gap by identifying determinants that may influence prognosis ICC after Methods conducted a study 172 patients who underwent hepatectomy between 2010 2019. evaluated demographics, tumor characteristics, whether were statin therapy. Kaplan–Meier methods used analyze overall (OS) recurrence‐free (RFS), whereas multivariate analysis was utilized identify prognostic factors. Results Statin use associated with significantly improved OS RFS. The mean 90.5 months in group compared 59.9 statin‐naive ( p = 0.001). Similarly, RFS longer (77.3 vs. 48.1 months; 0.006). Subgroup analyses demonstrated consistent benefits across different age groups genders. Multivariate identified as an independent factor (HR: 0.49, 95% CI: 0.29–0.82, 0.007) 0.60, 0.36–0.98, 0.043). Conclusions therapy be potentially favorable medication undergoing ICC. further evaluation its required, additional studies are recommended.

Language: Английский

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Cholesterol Metabolism in Pancreatic Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(21), P. 5177 - 5177

Published: Oct. 27, 2023

Pancreatic cancer's substantial impact on cancer-related mortality, responsible for 8% of cancer deaths and ranking fourth in the US, persists despite advancements, with a five-year relative survival rate only 11%. Forecasts predict 70% surge new cases 72% increase global pancreatic by 2040. This review explores intrinsic metabolic reprogramming cancer, focusing mevalonate pathway, including cholesterol biosynthesis, transportation, targeting strategies, clinical studies. The central to cellular metabolism, significantly shapes progression. Acetyl coenzyme A (Acetyl-CoA) serves dual role fatty acid fueling acinar-to-ductal metaplasia (ADM) intraepithelial neoplasia (PanIN) development. Enzymes, acetoacetyl-CoA thiolase, 3-hydroxy-3methylglutaryl-CoA (HMG-CoA) synthase, HMG-CoA reductase, are key enzymes cancer. Inhibiting e.g., using statins, shows promise delaying PanIN progression impeding Dysregulation modification, uptake, transport impacts tumor progression, Sterol O-acyltransferase 1 (SOAT1) driving ester (CE) accumulation disrupted low-density lipoprotein receptor (LDLR) expression contributing recurrence. Apolipoprotein E (ApoE) stroma influences immune suppression. Clinical trials statins SOAT1 inhibitors, exhibit potential anti-tumor effects, combination therapies enhance efficacy. provides insights into metabolism's convergence shedding light therapeutic avenues ongoing investigations.

Language: Английский

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