Researchers at the Hebrew University of Jerusalem, the California Institute of Technology and the David Geffen School of Medicine at UCLA have achieved a breakthrough in understanding how and why a promising anti-cancer therapy has failed to achieve hoped-for success in killing tumor cells.
The researchers looked at the problematic therapy involving suppression of the protein mTOR (mammalian target Of Rapamycin). MTOR plays an important role in regulating how cells process molecular signals from their environment, and it is observed as strongly activated in many solid cancers.
Drug-induced suppression of mTOR has until now shown success in causing the death of cancer cells in the outer layers of cancerous tumors, but has been disappointing in clinical trials in dealing with the core of those tumors.
The research team, which included Prof. Emeritus Raphael D. Levine of the Institute of Chemistry at the Hebrew University of Jerusalem and researchers from the California Institute of Technology and the David Geffen School of Medicine at UCLA, investigated whether the influence of hypoxia — reduced oxygen supply — on mTOR signaling in model brain cancer systems could explain the poor performance of mTOR drugs.
They found that at a particular level of hypoxia that is common in solid tumors, the mTOR signaling network switches between two sets of properties. At the switching point, the theoretical models predicted that mTOR would be intrinsically unresponsive to drugging.
The findings appeared in a recent article in the Proceedings of the National Academy of Sciences (PNAS) in the US.