Academic Journal
Main Category: Cancer / Oncology
Article Date: 24 Jun 2013 - 9:00 PDT Current ratings for:
Why Does Promising Anti-Cancer Therapy Suddenly Stop Working?
Why does anti-cancer therapy stop working at a specific stage? Scientists in Israel and the USA believe they have made a breakthrough in understanding why a hopeful anti-cancer therapy fails to destroy tumor cells successfully.
The researchers, whose study is published in PNAS (Proceedings of the National Academy of Sciences), believe their findings may lead to new approaches in overcoming this cul-de-sac.
Suppressing the mTOR (mammalian target Of Rapamycin) protein has been extremely challenging for oncologists.
mTOR plays a key role in regulating vital cell growth processes - it is a bit like a communications command center, receiving external signals from hormones, growth factors and proteins. It then sends out "on" or "off" signals for the cell to grow and divide, seek nutrition, or use that nutrition. mTOR is strongly activated in several solid cancers.
While drugs have been shown to suppress mTOR and have been successful in causing the death of cancer cells in the outer layers of malignant tumors, in clinical trials they have failed in destroying the core of those tumors.Hypoxia (lack of oxygen) is an almost-universal characteristic of solid tumors that can affect how tumors respond to therapies. Scientists know that the condition of hypoxia affects the behavior of mTOR signaling, but nobody knew what the mechanism was.
Prof. Emeritus Raphael D. Levine, from the Institute of Chemistry at the Hebrew University of Jerusalem, Israel, and scientists from the David Geffen School of Medicine at UCLA and the California Institute of Technology set out to determine what role hypoxia plays on mTOR signaling in model brain cancer systems and whether this could explain why promising mTOR drugs fail.
They used a new microchip technology to measure the mTOR protein-signaling network in cancer cells. They also used a new set of theoretical tools derived from the physical sciences to interpret the results. This dual approach simplified an otherwise extremely complex biological system.
The mTOR biochemical pathway is a complex one
The investigators found that at a specific level of hypoxia, which is typical in solid tumors, the mTOR signaling network switches between two sets of properties. At exactly the moment when the switching over takes places, the theoretical models predicted that mTOR would not respond to mTOR-inhibiting medications.
According to the combined experiment finding, the researchers believe that the switching over might be a kind of phase transition, something not observed before in biological systems.
This phase transition happened very suddenly, and cells being studied stopped responding like they had done before. The authors wrote "In the case of the tumor, the 'drugging' of the mTOR ceased, meaning that the tumor was no longer inhibited."
These results: explain why promising mTOR-inhibiting drugs stop working at a specific stage"indicate that certain complex biological behaviors, which often confound scientists who are seeking to find effective therapies for human diseases, may be understood by the effective application of experimental and theoretical tools derived from the physical sciences."Levine wrote in the PNAS Abstract:
"We find a hypoxia-induced switch within a mammalian target of rapamycin (mTOR) signaling network. At the switching point, mTOR is predicted, and then shown by experiment, to be unresponsive to inhibition. These results may help explain the undistinguished performance of mTOR inhibitors in certain clinical trials."
In an animal study, scientists from the University of California San Diego, La Jolla, found that mTOR-inhibitors may have adverse effects on heart function in patients with ongoing heart problems.
Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
MLA
24 Jun. 2013.
Please note: If no author information is provided, the source is cited instead.
posted by Greg Pawelski on 24 Jun 2013 at 12:17 pm
One of the themes at the 103rd Annual American Association of Cancer Research was the growing recognition that human tumors exist as microenvironments and not isolated single cells. The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. Each of these microenvironment factors has been shown to cause severe disturbance in cell metabolism and physiology.
By examining drug-induced cell death events in native-state 3D (three dimensional) microclusters, the functional profiling platform has the unique capacity to capture stromal, cytokines (chemokines), macrophages, lymphocytes, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction.
The microclusters recapitulate the human tumor environment, while the "3D" advancement recreates the extracellular matrix (metalloproteinases). The platform studies cancer response to drugs within this microenvironment, enabling it to provide clinically relevant predictions to cancer patients. It is this capacity to study human tumor microenvironments that distinguishes it from other platforms in the field.
Tumors are very complex organisms. Ignoring this complexity, most studies of human cancer in culture have focused upon individual tumor cells that have been removed from their complex microenvironment.
| post followup | alert a moderator |
'Why Does Promising Anti-Cancer Therapy Suddenly Stop Working?'
Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.
If you write about specific medications or operations, please do not name health care professionals by name.
All opinions are moderated before being included (to stop spam)
Contact Our News Editors
For any corrections of factual information, or to contact the editors please use our feedback form.
Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
No comments:
Post a Comment