Many cancers have changes in signaling pathways that control cell growth and survival. The PI3K–mTOR–Akt pathway is the most commonly altered, and at its center is the protein mTOR. mTOR functions as the engine for two distinct protein complexes, mTORC1 and mTORC2, and each complex has different roles for the cell.
Most drugs that target mTOR act on both mTORC1 and mTORC2. Taylor and colleagues note a key problem: shutting down mTORC1 can unintentionally make cancer cells more resistant to chemotherapy, reducing the benefit of nonselective inhibitors.
The study published in Science shows how mTORC2 recognizes its targets and suggests it should be possible to block only mTORC2 while leaving mTORC1 functional. Selective blockage of mTORC2 could stop growth signals that cancer cells use without triggering survival pathways. The researchers say they are working on drug designs that focus on the cancer-relevant side of the pathway.
Difficult words
- signaling — cell communication by chemical or molecular messages
- pathway — series of steps that control cell processespathways
- complex — group of proteins that work togethercomplexes
- inhibitor — drug or molecule that slows or stops activityinhibitors
- resistant — not affected or killed by a treatment
- recognize — to identify or bind a specific moleculerecognizes
- block — to stop or prevent a process happening
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Discussion questions
- Do you think drugs that block only mTORC2 would be safer for patients? Why or why not?
- What difficulties might scientists meet when designing drugs that target only one complex?
- How would stopping growth signals without triggering survival pathways change cancer treatment?
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