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The mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that plays a critical role in regulating cellular processes such as growth, proliferation, and metabolism in healthy cells. Dysregulation of mTOR signaling and oxidative stress have been implicated in various diseases including cancer. This review aims to provide an overview of the current understanding of mTOR and its involvement in cell survival and the regulation of cancer cell metabolism as well as its complex interplay with reactive oxygen species (ROS). On the one hand, ROS can inhibit or activate mTOR pathway in cancer cells through various mechanisms. Conversely, mTOR signaling can induce oxidative stress in tumor cells notably due to the inhibition in the expression of antioxidant enzyme genes. Since mTOR is often activated and plays crucial role in cancer cell survival, the use of mTOR inhibitors, which often induce ROS accumulation, could be an interesting approach for cancer treatment. This review will address the advantages, disadvantages, combination strategies, and limitations associated with therapeutic modulation of mTOR signaling pathway in cancer treatment.
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http://dx.doi.org/10.1016/j.bcp.2024.116729 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
Proc Natl Acad Sci U S A
September 2025
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8577, Japan.
All organisms are exposed to various stressors, which can sometimes lead to organismal death, depending on their intensity. While stress-induced organismal death has been observed in many species, the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms of stress-induced organismal death in the fruit fly .
View Article and Find Full Text PDFArch Pharm Res
September 2025
Department of Biosciences, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, West Bengal, 700109, India.
Bacoside A (BCA), a triterpenoid saponin isolated from Bacopa monnieri, exhibits diverse pharmacological properties, including neuroprotective, hepatoprotective, anti-stress, anti-inflammatory, and anti-ulcer effects. In the present study, BCA demonstrates pronounced anticancer activity against K562 chronic myelogenous leukemia (CML) cells by modulating autophagy-apoptosis dynamics. BCA induces dose- and time-dependent cytotoxicity in K562 cells while sparing normal human peripheral blood mononuclear cells (hPBMCs) and Vero cells, indicating therapeutic selectivity.
View Article and Find Full Text PDFG Ital Nefrol
August 2025
UO Nefrologia e Dialisi, Ospedale di Cassino, Italia.
SGLT-2 inhibitors are a relatively new class of antidiabetic drugs. They activate a transcriptional response similar to calorie restriction characterized by the up-regulation of sensors involved in nutrient deprivation, such as SIRT1 and AMPK, and the down-regulation of mTOR, a molecule involved in nutritional excess signaling. The purpose of this review is to illustrate the main pathways of nutrient deprivation: a complex mechanistic framework partly responsible for the cardio-renal benefits that makes these drugs unique.
View Article and Find Full Text PDFCancer Med
September 2025
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Background: Esophageal squamous cell carcinoma (ESCC) represents an aggressive cancer type associated with poor prognosis, often treated with neoadjuvant chemotherapy (NAC) using cisplatin-based regimens. However, cisplatin resistance limits therapeutic efficacy, necessitating a deeper understanding of resistance mechanisms. L-type amino acid transporter 1 (LAT1) plays a crucial role in amino acid uptake and is linked to cancer cell survival through activation of the mammalian target of rapamycin (mTOR) pathway.
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