Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Integration of cell survival signals in PTEN-deficient tumors

18.10.2005


Combined therapy is good for BAD



A new research study published in the October issue of Cancer Cell identifies a molecular switch that integrates cell survival signals from multiple intracellular signaling pathways. The finding has substantial clinical significance, as mutations in these cell survival-signaling pathways are associated with many human cancers, and a better understanding of how these pathways converge to regulate the delicate balance between cell proliferation and cell death may lead to development of more effective cancer therapies.

A complex interplay between growth signals and apoptosis (programmed cell death) regulates cell proliferation. Activation of the epidermal growth factor receptor (EGFR) inhibits apoptosis, and EGFR mutations are associated with some human cancers. However, inhibition of EGFR expression has not been widely successful as a cancer treatment because, in many cases, mutations occur in signaling molecules downstream of EGFR, such as the tumor suppressor PTEN. Dr. Neal Rosen and colleagues from Memorial Sloan-Kettering Cancer Center in New York examined interplay between cell proliferation signals in tumor cells with PTEN mutations.


The loss of the PTEN tumor suppressor gene results in constitutive activation of Akt, a molecule that promotes cell survival independently of EGFR. Tumor cells with mutated PTEN did not respond to treatment with EGFR inhibitors, but when PTEN activity was restored, tumor cells were sensitized to treatment with EGFR inhibitors. Importantly, both EGFR and Akt inhibit the activity of BAD, a molecule that drives apoptosis, and activation of either EGFR or Akt alone is sufficient to inhibit BAD and block cell death. The researchers further demonstrated that mice with tumors displaying PTEN mutations did not respond to either EGFR or Akt inhibition alone but that combined therapy resulted in significant tumor regression.

The results indicate that BAD acts as a switch that integrates the antiapoptotic effects of multiple pathways enhancing cell survival in PTEN-deficient tumor cells. "The data provide a heuristic model for understanding pathway interactions that allows the development of rational strategies for combination therapy and reveals a potential clinical role for inhibition of wild-type EGFR. Thus, EGFR inhibitors may be useful in combination with inhibitors of PI3K/Akt kinase signaling for the treatment of glioblastomas, prostate cancer, and other tumors in which EGFR activation and PTEN mutation coexist," explains Dr. Rosen

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com
http://www.cancercell.org

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>