This 2019 experimental study investigates how inhibition of the mammalian target of rapamycin (mTOR) pathway impedes colon cancer progression. The findings reveal that mTOR inhibition leads to the dephosphorylation of 4E-BP1, resulting in suppressed activity of eukaryotic translation initiation factor 4E (eIF4E). This suppression upregulates the expression of PUMA (p53
This 2022 review explores the complex role of metformin, a widely used antidiabetic agent, in cancer therapy. Metformin activates the AMPK pathway and inhibits mitochondrial complex I, leading to reduced ATP production and downstream inhibition of mTOR and PI3K/AKT signaling pathways. These actions result in decreased tumor cell proliferation and
This 2014 preclinical study investigates the combined effects of metformin and tamoxifen on estrogen receptor-positive (ER+) breast cancer cells. The combination therapy significantly inhibited cell proliferation, DNA replication, colony formation, and induced apoptosis more effectively than either agent alone. Mechanistically, the enhanced effects are associated with activation of the AMPK
This preclinical study explores the anti-cancer effects of artesunate (ART), a derivative of artemisinin traditionally used for malaria, in ovarian cancer models. ART was shown to suppress growth of multiple ovarian cancer cell lines and patient-derived primary cells, and to inhibit tumor progression in xenograft mouse models. The treatment significantly
This 2016 review highlights metformin’s potential as a geroprotective agent beyond its established use in type 2 diabetes management. The authors discuss metformin’s mechanisms, including activation of AMPK, inhibition of mTOR signaling, reduction of oxidative stress, and modulation of inflammatory responses. These actions collectively contribute to improved metabolic health and
This 2019 opinion article by Matt Kaeberlein and Veronica Galvan advocates for initiating clinical trials to assess rapamycin’s efficacy in treating Alzheimer’s disease (AD). Despite compelling preclinical evidence demonstrating rapamycin’s benefits in animal models—such as reducing amyloid-beta and tau pathology, improving cognitive function, and enhancing synaptic plasticity—no human trials had
This 2019 opinion article by Carosi and Sargeant evaluates the dualistic role of rapamycin in Alzheimer’s disease (AD) treatment. While early intervention with rapamycin in animal models has shown reductions in amyloid-beta and tau pathology, the authors caution against its use in later stages of AD. They argue that in
This 2013 study investigated the effects of chronic rapamycin treatment in transgenic mice exhibiting Alzheimer’s-like symptoms. Administered after symptom onset, rapamycin significantly restored cerebral blood flow, increased vascular density, reduced amyloid plaque accumulation, and minimized microhemorrhages. These effects were mediated by activation of endothelial nitric oxide synthase (eNOS), enhancing nitric
This 2018 pilot study assessed the safety and feasibility of daily 1 mg rapamycin administration over 8 weeks in 25 healthy older adults aged 70–95. The treatment was generally well-tolerated, with minor adverse events including facial rash, stomatitis, and gastrointestinal discomfort. Notably, there were statistically significant reductions in erythrocyte parameters
This 2018 hypothesis article proposes that low-dose mTOR inhibition, particularly with rapamycin, may slow the progression of low-grade prostate cancer, enabling patients to remain on active surveillance and avoid or delay definitive treatments like surgery or radiation. The rationale is based on mTOR’s role in cellular senescence and immunomodulation, especially
