Signaling pathways let cells communicate and respond to their environment. The PI3K–mTOR–Akt pathway is the one most often altered in cancer, and mTOR sits at its center. What makes mTOR unusual is that it acts as the engine for two distinct complexes, mTORC1 and mTORC2. Each complex performs a different set of functions, and those differences matter for treatment choices.
Most mTOR-targeting drugs affect both mTORC1 and mTORC2. Taylor and his colleagues point out a key limitation of that approach: inhibiting mTORC1 can have an unintended effect by making cancer cells more resistant to chemotherapy, which reduces the overall benefit of nonselective inhibitors.
In research published in Science, the team studied how mTORC2 finds and recognizes its targets. Their results indicate it should be possible to block only mTORC2 while keeping mTORC1 functional. According to the report, selective blockade of mTORC2 can shut down growth signals used by cancer cells without triggering the survival pathways linked to mTORC1 inhibition. The researchers, including Martin Taylor at Brown University, say they are already working on drug designs that act on the cancer-relevant side of the pathway. Taylor commented, "This helps point the way toward designing drugs that target the cancer-relevant side of the pathway without triggering survival pathways that protect the tumor." He also said the work answers open questions important for basic biology and has therapeutic implications. The research announcement came from Brown University and appeared on Futurity.
Difficult words
- pathway — series of events that produce a resultpathways
- complex — a group of proteins that work togethercomplexes
- inhibit — to stop or slow a biological processinhibiting
- resistant — not easily affected or harmed by treatment
- nonselective — affecting multiple targets rather than one
- blockade — an action that prevents a process or access
- therapeutic — related to treatment or medical care
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How might drugs that target only mTORC2 change choices in cancer treatment? Give reasons.
- What difficulties do you think researchers could face when designing drugs that act only on mTORC2?
- Compare possible advantages and disadvantages of nonselective inhibitors versus selective mTORC2 inhibitors.
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