• cancer
• diseases

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Male
• Female
• Middle Aged
• Head and Neck Neoplasms/mortality
• Head and Neck Neoplasms/drug therapy
• Head and Neck Neoplasms/diagnosis
• Squamous Cell Carcinoma of Head and Neck/mortality
• Aged
• Cohort Studies
• Universal Health Care
• United States/epidemiology
• Adult
• Proportional Hazards Models

• United States Department of Defense | Uniformed Services University of the Health Sciences (Uniformed Services University)

• diseases
• medical research

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Retrospective Studies
• Cohort Studies
• Head and Neck Neoplasms/drug therapy
• Head and Neck Neoplasms/epidemiology
• Prognosis
• Multicenter Studies as Topic

• Korea Health Industry Development Institute
• Ministry of Health & Welfare

• case-control studies
• epidemiology
• esophageal cancer
• risk factors
• statins

• RS-2023-00208042 National Research Foundation of Korea

• Esophageal carcinoma
• Prognosis
• TCGA
• Tumor immunity

• esophageal cancer
• meta-analysis
• prognosis
• statin
• survival

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Retrospective Studies
• Prospective Studies
• Esophageal Neoplasms
• Prognosis
• Neoplasms, Second Primary

• esophageal cancer
• esophagectomy
• obesity
• statins

Tongue cancer is one of the most common carcinomas of the head and neck region. The antitumor activities of statins, including lovastatin (LV), and the essential oil of eucalyptus (Eu oil), have been adequately reported. The aim of this study was to develop a nanoemulgel containing LV combined with Eu oil that could then be made into a nanoemulsion and assessed to determine its cytotoxicity against the cell line human chondrosarcoma-3 (HSC3) of carcinoma of the tongue. An I-optimal coordinate-exchange quadratic mixture design was adopted to optimize the investigated nanoemulsions. The droplet size and stability index of the developed formulations were measured to show characteristics of the nanoemulsions. The optimized LV loaded self-nanoemulsifying drug delivery system (LV-Eu-SNEDDS) was loaded into the gelling agent Carbopol 934 to develop the nanoemulgel and evaluated for its rheological properties. The cytotoxic efficiency of the optimized LV-Eu-SNEDDS loaded nanoemulgel was tested for cell viability, and the caspase-3 enzyme test was used against the HSC3 cell line of squamous carcinoma of the tongue. The optimized nanoemulsion had a droplet size of 85 nm and a stability index of 93%. The manufactured nanoemulgel loaded with the optimum LV-Eu-SNEDDS exhibited pseudoplastic flow with thixotropic behavior. The developed optimum LV-Eu-SNEDDS-loaded nanoemulgel had the best half-maximal inhibitory concentration (IC₅₀) and caspase-3 enzyme values of the formulations developed for this study, and these features improved the ability of the nanoemulsion-loaded gel to deliver the drug to the investigated target cells. In addition, the in vitro cell viability studies revealed the synergistic effect between LV and Eu oil in the treatment of tongue cancer. These findings illustrated that the LV-Eu-SNEDDS-loaded gel formulation could be beneficial in the local treatment of tongue cancer.

Studies have shown that obesity is associated with many adverse health effects, including worse cancer outcomes. Many studies paradoxically suggest a survival benefit for obesity in treatment outcomes of cancers such as non-small-cell lung cancer. This relationship is not seen in animal models. We hypothesize that this relationship is secondary to suboptimal quantification of adiposity, enhanced immunotherapy response, and variables such as sex, medications, and smoking status. There are many ways to measure and classify adiposity, but the ability to distinguish abdominal obesity is likely key in predicting accurate prognosis. There are many ways obesity impacts cancer treatment course from diagnosis to survivorship. In this paper, we aim to analyze the factors contributing to the obesity paradox and its effect on lung cancer. This can aid the treatment and prognosis of lung cancer and may support further research into obesity-specific impacts on this malignancy.

There is a paradoxical relationship between obesity, as measured by BMI, and many types of cancer, including non-small-cell lung cancer. Obese non-small-cell lung cancer patients have been shown to fare better than their non-obese counterparts. To analyze the multifaceted effects of obesity on oncologic outcomes, we reviewed the literature on the obesity paradox, methods to measure adiposity, the obesity-related derangements in immunology and metabolism, and the oncologic impact of confounding variables such as gender, smoking, and concomitant medications such as statins and metformin. We analyzed how these aspects may contribute to the obesity paradox and cancer outcomes with a focus on lung cancer. We concluded that the use of BMI to measure adiposity is limited and should be replaced by a method that can differentiate abdominal obesity. We also concluded that the concomitant metabolic and immunologic derangements caused by obesity contribute to the obesity paradox. Medications, gender, and smoking are additional variables that impact oncologic outcomes, and further research needs to be performed to solidify the mechanisms.

Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, and are widely used as an effective and safe approach handle hypercholesterolemia. The mevalonate pathway is a vital metabolic pathway that uses acetyl-CoA to generate isoprenoids and sterols that are crucial to tumor growth and progression. Multiple studies have indicated that statins improve patient prognosis in various carcinomas. Basic research on the mechanisms underlying the antitumor effects of statins is underway. The development of new anti-cancer drugs is progressing, but increasing medical costs from drug development have become a major obstacle. Readily available, inexpensive and well-tolerated drugs like statins have not yet been successfully repurposed for cancer treatment. Identifying the cancer patients that may benefit from statins is key to improved patient treatment. This review summarizes recent advances in statin research in cancer and suggests important considerations for the clinical use of statins to improve outcomes for cancer patients.

• Statin
• HMG CoA reductase inhibitor
• Mevalonate pathway
• Cancer

Esophageal adenocarcinoma (EAC) is a highly lethal cancer with rising incidence in Western countries. Despite diagnostic and therapeutic advances, average 5-year EAC survival remains poor (~20%), with tumor stage and treatment the strongest prognostic factors. The role of lifestyle-related exposures remains uncertain. To address this gap, we analyzed survival associations among EAC patients treated at a tertiary cancer center. Importantly, this study is among the first to assess survival relationships by disease stage for several key lifestyle-related exposures (e.g., physical activity, medications, and diet), enabling us to identify associations which may have been obscured in past analyses. Our findings suggest that lifestyle interventions such as smoking cessation, exercise regimens, and use of cholesterol-lowering (statin) or anti-inflammatory (NSAID) medications may represent promising avenues to improve outcomes in this deadly cancer.

Purpose: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. Methods: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan–Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. Results: Among patients presenting with localized/regional tumors (stages I–III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42–4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35–0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42–0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42–0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. Conclusion: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.

• esophageal adenocarcinoma
• lifestyle factors
• prognosis
• survival

• Clinical outcomes
• Clinical studies
• Esophageal cancer
• Preclinical studies
• Statins

• HMG-CoA reductase
• SREBP-2
• cancer therapy
• cholesterol
• mevalonate

• cancer specific mortality
• hmg-coa inhibitors
• recurrence
• statin

• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Male
• Neoplasms/drug therapy
• Neoplasms/mortality
• Observational Studies as Topic
• Prognosis
• Progression-Free Survival
• Proportional Hazards Models
• Survival Rate
• Treatment Outcome

• Adenocarcinoma/drug therapy
• Adenocarcinoma/mortality
• Aged
• Chemotherapy, Adjuvant
• Cholesterol, LDL/blood
• Cholesterol, LDL/drug effects
• Combined Modality Therapy
• Double-Blind Method
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/mortality
• Esophagectomy
• Feasibility Studies
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
• Male
• Medication Adherence/statistics & numerical data
• Middle Aged
• Quality of Life
• Simvastatin/administration & dosage
• Simvastatin/adverse effects
• Treatment Outcome
• United Kingdom

• DRF-2013-06-115 Department of Health
• Research Trainees Coordinating Centre

• Statins
• cancer
• cancer therapeutics
• cellular and molecular cancer
• clinical outcomes

• Liver Cancer
• Medication Use
• Prognosis
• VA

Purpose: Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductases, are designed to treat lipid disorders, especially hypercholesterolemia. Apart from their role in preventing heart diseases in patients with high cholesterol, recent evidence suggests that statins have anti-tumor properties. However, studies assessing the association between statin use and esophageal cancer survival outcomes have provided controversial results.

Methods: We conducted a systematic review and meta-analysis focusing on studies evaluating associations between statin use and survival outcomes for esophageal cancer patients.

Results: A total of five cohort studies comprising 24,576 patients were included. Statin use associated with improved overall survival (OS: HR 0.84, 95% CI, 0.75–0.94) and disease-free survival (DFS: HR 0.84, 95% CI, 0.75–0.96) of esophageal cancer patients. The improved survival outcomes were consistent in the esophageal adenocarcinoma subgroup and the esophageal squamous cell cancer subgroup.

Conclusion: A potential therapeutic role of statins in esophageal cancer has been demonstrated in our study, however, the results should be interpreted cautiously and need further confirmation by future studies.

• drug repositioning
• esophageal cancer
• statins
• survival outcome

• Epidemiology
• Esophageal cancer
• Pharmacoepidemiology
• Statin
• Survival

The mevalonate pathway provides sterols for membrane structure and nonsterol intermediates for the post-translational modification and membrane anchorage of growth-related proteins, including the Ras, Rac, and Rho GTPase family. Mevalonate-derived products are also essential for the Hedgehog pathway, steroid hormone signaling, and the nuclear localization of Yes-associated protein and transcriptional co-activator with PDZ-binding motif, all of which playing roles in tumorigenesis and cancer stem cell function. The phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-mammalian target of rapamycin complex 1 pathway, p53 with gain-of-function mutation, and oncoprotein MYC upregulate the mevalonate pathway, whereas adenosine monophosphate-activated protein kinase and tumor suppressor protein RB are the downregulators. The rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is under a multivalent regulation. Sterol regulatory element binding protein 2 mediates the sterol-controlled transcriptional downregulation of HMGCR. UbiA prenyltransferase domain-containing protein-1 regulates the ubiquitination and proteasome-mediated degradation of HMGCR, which is accelerated by 24, 25-dihydrolanosterol and the diterpene geranylgeraniol. Statins, competitive inhibitors of HMGCR, deplete cells of mevalonate-derived intermediates and consequently inhibit cell proliferation and induce apoptosis. Clinical application of statins is marred by dose-limiting toxicities and mixed outcomes on cancer risk, survival and mortality, partially resulting from the statin-mediated compensatory upregulation of HMGCR and indiscriminate inhibition of HMGCR in normal and tumor cells. Tumor HMGCR is resistant to the sterol-mediated transcriptional control; consequently, HMGCR is upregulated in cancers derived from adrenal gland, blood and lymph, brain, breast, colon, connective tissue, embryo, esophagus, liver, lung, ovary, pancreas, prostate, skin, and stomach. Nevertheless, tumor HMGCR remains sensitive to isoprenoid-mediated degradation. Isoprenoids including monoterpenes (carvacrol, L-carvone, geraniol, perillyl alcohol), sesquiterpenes (cacalol, farnesol, β-ionone), diterpene (geranylgeranyl acetone), “mixed” isoprenoids (tocotrienols), and their derivatives suppress the growth of tumor cells with little impact on non-malignant cells. In cancer cells derived from breast, colon, liver, mesothelium, prostate, pancreas, and skin, statins and isoprenoids, including tocotrienols, geraniol, limonene, β-ionone and perillyl alcohol, synergistically suppress cell proliferation and associated signaling pathways. A blend of dietary lovastatin and δ-tocotrienol, each at no-effect doses, suppress the growth of implanted murine B16 melanomas in C57BL6 mice. Isoprenoids have potential as adjuvant agents to reduce the toxicities of statins in cancer prevention or therapy.

• HMG CoA reductase
• SREBP
• cancer
• isoprenoids
• mevalonate
• statin
• synergy

• Adenocarcinoma
• Aspirin
• Barrett Esophagus
• Esophageal Neoplasms
• Esophagus
• Humans
• Proton Pump Inhibitors