Why anti-cancer treatment fails to work at a some point
Researchers at the Hebrew University of Jerusalem and in California have made important discoveries about cancer treatment. These findings came after they understood why a cancer treatment that involves the protein mTOR (mammalian target of rapamycin) failed in destroying tumor cells.
The study results published in the Proceedings of the National Academy of Sciences (PNAS) in the U.S., have several important implications in cancer therapy. First of all, the study explains why mTOR inhibitors in cancer treatment do not work. Apart from this, the study shows that complex biological behaviors can be better understood if the interpretation of the results would take into account theoretical tools derived from the physical sciences.
The therapy that failed involved the suppression of the protein mTOR (mammalian target of rapamycin), a protein that regulates signals from outside the cell. Since researchers have observed that mTOR is activated in many solid cancers, this protein has been considered a promising therapeutic target in cancer treatment. The therapy based on the suppression of mTOR has worked in the destruction of tumor cells in the external layers of the tumor, but it has not have the same effect on the core of the tumor. It is already known that hypoxia, which means lack of oxygen, influences how tumors respond to cancer treatment. It is also known that mTOR signaling is affected and altered by hypoxia, but researchers could not elucidate the link between hypoxia and mTOR and why this happen.
A team of researchers, led by Professor 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 may explain the poor result of drugs that inhibit mTOR in brain cancer model systems. They measured the protein mTOR signaling network in cancer cells using a new microchip technology and compared the results with a set of theoretical tools.
It seems that the combination of theoretical and experimental results led to some observations that could not be detected in biological systems. In this way they could find out that at a certain level of hypoxia, mTOR signaling network changes, which means that drugs that inhibit mTOR are no longer effective. It seems that this phase transition occurs very abruptly. This change in signaling means the cell body does not respond to treatment anymore and if the drugs that inhibit mTOR are no longer effective, the cancer cannot be cured.