Discovery of a cancer promoter offers pathway to overcome drug resistance
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IMAGE: A chance experiment in the Grosveld laboratory hinted that a third mTOR complex might exist that was assembled by a protein called ETV7. view more 

Credit: St. Jude Children’s Research Hospital

Geneticists at St. Jude Children’s Research Hospital have discovered a previously unknown cell growth mechanism that makes a wide range of cancers resistant to rapamycin and related drugs. The finding offers the promise of new drug therapies that can overcome that resistance to treat cancers including leukemia and tumors in the brain and other organs.

The researchers, led by Gerard Grosveld, Ph.D., member and chair of the Department of Genetics, published their findings as an advance online publication of the journal Science Advances.

The enzyme mTOR is a central regulator of cell growth and is often abnormally activated in many cancers to drive their proliferation. The drug rapamycin and its close relatives, called rapalogs, are known to plug into the mTOR molecule to block its action. However, the drugs have proven only marginally effective against cancers, because most are resistant to the drugs.

Researchers had known that the mTOR enzyme was controlled in its many functions by being embedded in two protein complexes, called mTORC1 and mTORC2.

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