mTORC1/2

Overview

mTORC1/2 refers to the two major mechanistic target of rapamycin complexes, mTOR complex 1 and mTOR complex 2. Together, these protein kinase assemblies integrate nutrient availability, growth factor signaling, cellular energy status, and stress responses to regulate fundamental processes such as protein synthesis, autophagy, metabolism, cytoskeletal organization, and cell survival. Because of this central role, dysregulation of mTOR signaling is implicated in cancer, metabolic disease, neurodegeneration, immune dysfunction, and tissue remodeling.

In biomedical research, mTORC1/2 is often discussed as a pathway node rather than a single isolated molecule, since many interventions affect both complexes or selectively modulate one arm of the pathway. Pharmacologically, this makes mTORC1/2 an important target for pathway-based therapies, including agents such as vistusertib and related PI3K/AKT/mTOR inhibitors, as well as compounds studied for indirect effects on mTOR signaling in diseases such as tuberous sclerosis complex, Metabolic dysfunction associated steatohepatitis, cervical cancer progression, inflammatory skin disease, and Alzheimer’s disease-related autophagy defects.

Focus of Latest Publications

Recent publications have examined mTORC1/2 as part of broader PI3K/AKT/mTOR signaling in diverse disease settings, most often in cancer and tissue repair. In endometrial cancer cells, verbascoside was investigated as a potential antitumor agent in the context of the LRIG2-PI3K/AKT/mTOR axis, with the study focused on apoptosis induction. In colorectal cancer, robinin was tested in a DMH-induced rat model and was reported to reduce tumor burden and precancerous lesions while diminishing inflammatory cytokines, histopathological damage, and apoptosis-related markers; these effects were linked to modulation of Ras/PI3K/Akt/mTOR and NF-κB/Bax/caspase-3 signaling. In cervical squamous cell carcinoma progression, integrated single-cell and spatial transcriptomic analyses identified ISG15-driven activation of the FGF1/FGFR1/PI3K/AKT/mTOR pathway, and both FGFR1 and PI3K/AKT/mTOR inhibitors suppressed cancer cell proliferation in vitro and tumor growth in vivo.

Other studies extended mTORC1/2-related signaling to nonmalignant and translational contexts. A protein hydrogel membrane for diabetic wound repair was reported to accelerate healing in a Staphylococcus aureus-infected diabetic wound model, with benefits attributed in part to activation of EGFR-associated PI3K/AKT/mTOR signaling alongside improved macrophage polarization and restoration of dermal architecture. In skeletal muscle atrophy induced by dexamethasone, phillyrin partially restored mTOR signaling together with PGC-1α signaling, while suppressing 15-PGDH and restoring prostaglandin E2/EP4 signaling; these changes were associated with reduced FOXO3a-mediated proteolysis and improved muscle mass and function.

Several recent papers also positioned mTORC1/2 as a therapeutic target in liver disease and other cancers. In metabolic dysfunction-associated steatohepatitis, vistusertib was studied as an mTORC1/2 inhibitor for the spectrum of liver disorders, with the stated goal of attenuating steatohepatitis and preventing hepatocellular carcinoma development. In hepatocellular carcinoma, Bie-Jia-Jian Pill was reported to inhibit tumor glycolysis and promote CD8+ cell-mediated antitumor immunity by targeting HIF-1α-PI3K/AKT/mTOR and CCL20. In classic Kaposi’s sarcoma, single-cell and spatial transcriptomics revealed mTOR-driven cellular fate of spindle cells and immune evasion, and the study assessed the therapeutic potential of the mTOR inhibitor metformin. Computational work in head and neck cancer likewise identified a metformin analogue with stable binding to mTOR, supporting continued interest in direct mTOR targeting across tumor types.

Outside oncology, mTOR-related signaling was also discussed in Marfan-associated thoracic aortic aneurysm and autism spectrum disorder. In aging Marfan mice, reduced Rictor expression and overall reduction of mTOR signaling were associated with late-term growth arrest of the aneurysm, suggesting that limiting mTOR activity may contribute to lesion stabilization. A review on pediatric autism highlighted abnormalities in mTOR/PI3K-AKT signaling among multiple implicated pathways and discussed nanotechnology-based drug delivery as a strategy to overcome the blood–brain barrier and enable future CNS-targeted interventions.

Key Publications

• NEWJul Targeting the LRIG2-PI3K/AKT/mTOR Axis to Induce Apoptosis: A Novel Antitumor Mechanism of Verbascoside in Endometrial Cancer Cells. (Anticancer research, 2026, PMID 42373282): "Targeting the LRIG2-PI3K/AKT/mTOR Axis to Induce Apoptosis: A Novel Antitumor Mechanism of Verbascoside in Endometrial Cancer Cells."
• NEWJul Robinin Attenuates Xenobiotic Enzymes, Inflammation, and Apoptosis on DMH-Induced Colon Cancer via Modulating Ras/PI3K/Akt/mTOR and NF-κB/Bax/Caspase-3 Signalling Pathways in Wistar Rats. (Journal of biochemical and molecular toxicology, 2026, PMID 42365609): "Targeting important signalling pathways, such as NF-κB and PI3K/Akt/mTOR/Ras, facilitated these results."
• NEWJun Investigation of metformin analogues in targeting signaling molecules of head and neck cancer pathways by computational approaches. (Scientific reports, 2026, PMID 42331865): "PubChem compound CID 222300 emerged as a top-scoring ligand with a high binding affinity for the mTOR protein (PDB: 4JSV)."
• NEWJan Nanotechnology-Driven Drug-Delivery Systems: Mechanistic Insights for Pediatric Autism Treatment in 2026. (International journal of nanomedicine, 2026, PMID 42292036): "Converging evidence implicates abnormalities in synaptic scaffolding and transmission, excitation-inhibition imbalance, mTOR/PI3K-AKT signaling, neuroinflammation, gut-brain axis, and metabolic disturbances, highlighting multiple cellular and molecular targets for potential therapeutic development."
• NEWJun Dual-enzyme cascade protein hydrogel membrane orchestrates metabolism-immunity coupling for diabetic wound repair. (Acta biomaterialia, 2026, PMID 42289263): "Concurrentl, GM/CEB activated EGFR-associated signaling pathways (PI3K/AKT/mTOR), thereby enhancing tissue regeneration and restoring dermal architecture."
• NEWJun Integrated multi-omics profiling of treatment-naive cervix uteri premalignant lesions and cervical squamous cell carcinoma reveals ecosystem and drivers underlying cervical cancer progression. (Cell death & disease, 2026, PMID 42265073): "Moreover, ISG15, synthesized by inflammatory cancer-associated fibroblasts (CAFs), enhances the stability of FGF1, thereby activating the FGF1/FGFR1/PI3K/AKT/mTOR signaling pathway."
• Jun Growth arrest of thoracic aortic aneurysms in aging Marfan mice. (American journal of physiology. Heart and circulatory physiology, 2026, PMID 42222959): "Although there is a need to better understand the interconnected roles of temporal changes in differential gene expression and protein abundance, modulating transforming growth factor-beta (TGF-β) signaling and reducing mTOR signaling appear to merit increased attention in limiting aneurysmal expansion in Marfan syndrome."
• May Targeting mTOR with vistusertib attenuates metabolic steatohepatitis and prevents HCC development. (Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026, PMID 42189199): "This study aimed to investigate the therapeutic effect of the mTORC1/2 inhibitor (vistusertib) against the spectrum of liver disorders."
• Jun Phillyrin attenuates dexamethasone-induced skeletal muscle atrophy by inhibiting 15-PGDH. (Biochemical and biophysical research communications, 2026, PMID 42000627): "These changes were associated with inhibition of FOXO3a-mediated proteolysis and partial restoration of mTOR and PGC-1α signaling in skeletal muscle."
• Mar Bie-Jia-Jian Pill: Inhibiting tumor glycolysis and promoting CD8+ cell-mediated anti-tumor immunity by targeting HIF-1α-PI3K/AKT/mTOR and CCL20 in hepatocellular carcinoma. (Journal of ethnopharmacology, 2026, PMID 41866005): "Bie-Jia-Jian Pill: Inhibiting tumor glycolysis and promoting CD8+ cell-mediated anti-tumor immunity by targeting HIF-1α-PI3K/AKT/mTOR and CCL20 in hepatocellular carcinoma."