Rapamycininsensitive

Rapamycininsensitive, often written rapamycin-insensitive, refers to elements of cellular signaling that are not inhibited by rapamycin, a macrolide drug that targets the mechanistic target of rapamycin (mTOR) pathway by binding FKBP12.

In the mTOR signaling network, two complexes exist: mTORC1 and mTORC2. Acute exposure to rapamycin inhibits mTORC1, but mTORC2 is often rapamycin-insensitive in the short term. Prolonged treatment with rapamycin can disrupt mTORC2 assembly in some cell types, leading to changes in downstream signaling. Because some pathways or outputs behave in a rapamycin-insensitive manner, they can sustain cellular growth or survival despite drug treatment.

The existence of rapamycin-insensitive elements has implications for research and therapy. Some cellular processes and signaling outputs under mTOR control may persist under rapamycin treatment, contributing to drug resistance or limited efficacy. To overcome these limitations, researchers employ ATP-competitive mTOR inhibitors that target the kinase domain of mTOR, or combine rapamycin with inhibitors of parallel pathways.

In research writing, rapamycininsensitive is used descriptively to characterize pathways, processes, or responses that are not suppressed by rapamycin. It is not a single protein or gene but a property of how particular components of the TOR signaling network respond to rapamycin across different cellular contexts.