mTORC1/2
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.