Cancer: New target found for drug-resistant tumors
ISLAMABAD: Rapamycin and drugs that act like it have a limited effect against many cancers because their tumors are resistant to them. Now, the discovery of a cell growth mechanism could lead to new drugs that overcome this resistance in some cancers.
The mechanism involves a previously unknown protein complex called mammalian target of rapamycin complex 3 (mTORC3).
Scientists at St. Jude Children's Research Hospital in Memphis, TN, came across it by chance when they were doing an experiment.
Their study is the subject of a paper that now features in the journal Science Advances.
"This new complex," explains senior study author Gerard C. Grosveld, who is the chair of the genetics department at the hospital, "has not been on anybody's radar screen, even though mTOR complexes have been studied for the last 25 years."
He and his team describe the finding as a "paradigm shift" in our understanding of an important cell growth mechanism and declare that it offers a "novel target for anti- cancer drug development."
The enzyme mammalian (or mechanistic) target of rapamycin (mTOR) plays a key role in the control of crucial cell processes; it regulates growth and keeps it in a state of equilibrium.
Abnormal activation of mTOR appears as a factor in an "increasing number" of diseases; as well as cancer, these include neurodegeneration, type, and obesity.
In cancer, abnormal mTOR activation promotes tumor growth. Rapamycin, as well as drugs that act like it — known as rapalogs — are designed to stop this by blocking mTOR.
Most rapalogs, however, have limited effect in cancer because tumor cells are resistant to them.
Scientists had already revealed that mTOR exerted its wide influence from within two large protein complexes: mTORC1 and
Grosveld and his team, however, recently came across evidence to suggest that there might be a third mTOR protein complex, and that a transcription factor protein called
ETV7 assembled it.