Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

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



comments powered by Disqus

Channels

Drug Discovery

view channel

Ibuprofen May Restore Immune Function in Older Individuals

New research suggests that macrophages from the lungs of old mice respond differently to infections than those of young mice, and ibuprofen given to the mice reversed these changes. New research using lab mice suggests that the solution to more youthful immune function might already be a common over-the-counter pain reliever.... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.