Phosphoinositide 3-kinase–mechanistic target of rapamycin signaling network (PI3K/mTOR)

The phosphoinositide 3-kinase–mechanistic target of rapamycin signaling network (PI3K/mTOR) refers to a highly integrated intracellular signaling cascade involving PI3K (phosphoinositide 3-kinase) and mTOR (mechanistic target of rapamycin), which together regulate many fundamental cellular processes, including cell growth, proliferation, metabolism, and survival[1][2][3][7]. PI3K is a lipid kinase activated downstream of various growth factor receptors, leading to the production of PIP3 and activation of AKT, another key signaling node. mTOR functions as a central kinase in two complexes (mTORC1 and mTORC2), integrating signals from PI3K/AKT as well as nutrients and growth factors[2][5][8]. The pathway is frequently activated in cancer and metabolic diseases, making both PI3K and mTOR important therapeutic targets. Numerous drugs targeting either or both pathway components have been developed for cancer and other indications. However, targeting this network poses safety and resistance challenges, and current drugs mostly inhibit the pathway rather than directly regulate a single receptor or enzyme, which complicates biomarker selection and toxicity management[4][7].\n\nNote:\n"is_incorrect: true" – The term "PI3K/mTOR" refers to a signaling network or pathway, not a single molecule or receptor. It is not a standalone protein or enzyme but rather encompasses at least two distinct targets—PI3K and mTOR. Structured target annotation should distinguish individual proteins (e.g., "Phosphoinositide 3-kinase catalytic subunit alpha" or "Mechanistic target of rapamycin"); "PI3K/mTOR" should only be used for pathway-level annotations or dual-target inhibitors[3][5].

Other names

PI3K-mTOR pathwayPI3K/AKT/mTOR pathwayphosphoinositide 3-kinase–mTOR pathwayPI3K/MTOR signalling network

Inhibition of mTOR kinase (mTORC1 and/or mTORC2) to suppress cell growth and proliferation; Inhibition of PI3K lipid kinase activity to prevent downstream activation of AKT, mTOR, and survival signals; Inhibition of pathway to induce apoptosis, block cell cycle, reduce metabolism; Dual PI3K/mTOR inhibition targeting both nodes for enhanced antitumor activity