Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Some Anticancer Drugs Stop Working at a Hypoxia-Induced Phase Transition Point

By BiotechDaily International staff writers
Posted on 27 Jun 2013
By applying physical science analytical techniques and a basic understanding of the principles of thermodynamics to the problem of drug resistance in cancer cells with mTOR (mammalian target of rapamycin) mutations, cancer researchers identified a hypoxia-induced phase transition point at which mTOR suppressing drugs were no longer effective.

Hypoxia is a near-universal feature of solid tumors, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. Similarly, it has been known that the behavior of mTOR signaling was influenced and altered by hypoxia, but the mechanism behind this was unknown.

Investigators at the Hebrew University of Jerusalem (Israel) and their colleagues at the California Institute of Technology (Pasadena, USA) and the University of California, Los Angeles (USA) worked with a glioblastoma multiforme (GBM) cancer cell model to examine the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2 (oxygen partial pressure). For this study, they employed a microchip technology that facilitated quantification of a panel of functional proteins from statistical numbers of single cells. Results were interpreted using a set of theoretical tools derived from the physical sciences, which enabled the simplification of an otherwise complex biological system.

Results published in the April 9, 2013, issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) revealed that near 1.5% pO2, the mTOR signaling network - a critical component of hypoxic signaling and a compelling cancer drug target - was deregulated in a manner such that it became unresponsive to mTOR kinase inhibitors. While being unresponsive to mTOR kinase inhibitors near 1.5% pO2, cancer cells did respond at higher or lower pO2 values. These findings were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor.

The investigators concluded that, "Our analysis—which may help explain the undistinguished performance of mTOR inhibitors in certain clinical trials—indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles."

Related Links:
Hebrew University of Jerusalem
California Institute of Technology
University of California, Los Angeles



Channels

Drug Discovery

view channel

Curcumin Used to Treat Alzheimer’s Disease

Curcumin, a natural substance found in the spice turmeric, has been used by many Asian cultures for centuries. Now, new research suggests that a close chemical analog of curcumin has properties that may make it useful as a treatment for Alzheimer’s disease. “Curcumin has demonstrated ability to enter the brain, bind... Read more

Biochemistry

view channel
Image: Induced pluripotent stem (iPS) cells, which act very much like embryonic stem cells, are shown growing into heart cells (blue) and nerve cells (green) (Photo courtesy of Gladstone Institutes/Chris Goodfellow).

Methodology Devised to Improve Stem Cell Reprogramming

In a study that provides scientists with a critical new determination of stem cell development and its role in disease, researchers have established a first-of-its-kind approach that outlines the stages... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.