Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inhibition of insulin-like growth factor receptor-1 as promising anticancer therapeutic

27.02.2004


Scientists report that an unlikely molecule has emerged as an attractive target for development of therapeutics aimed at a diverse spectrum of tumors, including some malignancies that are resistant to conventional therapies. Two studies published online in Cancer Cell demonstrate that the insulin-like growth factor 1 receptor (IGF-1R) is required for the survival of tumor cells and provide direct evidence that inhibition of IGF-R1 using selective small molecules represents a novel potential anticancer treatment.



Extensive studies have suggested that IGF-1R plays a role in the development of human cancers. IGF-1R is present in a broad range of tumor types including multiple myeloma, lymphoma, leukemia, and breast, lung, prostate, and colon cancers. However, IGF-1R has not been viewed as a likely target for cancer therapeutics because many normal cells also contain the protein. Research scientists from Dana-Farber Cancer Institute in Boston and Novartis Institutes for Biomedical Research Basel demonstrate that IGF-1R inhibition using a variety of methods had potent antitumor effects against many types of cancer cells grown in the laboratory, including cells that are resistant to conventional cancer therapeutics.

Molecular analyses demonstrated that IGF-1R inhibition impacts multiple intracellular signals related to cell proliferation or tumor development and provides possible mechanisms to explain how IGF-1R inhibition can make tumor cells more sensitive to conventional chemotherapy or other anticancer agents. Perhaps most significantly, IGF-1R suppresses tumor growth, prolongs survival, and enhances the antitumor effect of chemotherapy in clinically relevant mouse models of multiple myeloma and other hematological malignancies. The researchers also identify two small molecules that are selective inhibitors of IGF-1R and are active anticancer agents against tumors that contain IGF-1R. These small molecules represent highly attractive potential therapeutics.


According to study author Dr. Constantine S. Mitsiades of Dana-Farber, "These results suggest that IGF-1R function is critically required for tumor cell survival, but dispensable for survival of normal cells in adult animals. The preclinical activity of IGF-1R inhibitors against a broad spectrum of tumor cells and, importantly, their ability to sensitize tumor cells to a wide range of anticancer agents, highlight the major role of IGF-1R signaling for human malignant cells, and suggest that the molecular pathway of IGF-1R is an attractive potential target for development of anticancer therapeutics."


Constantine S. Mitsiades, Nicholas S. Mitsiades, Ciaran J. McMullan, Vassiliki Poulaki, Reshma Shringarpure, Masaharu Akiyama, Teru Hideshima, Dharminder Chauhan, Marie Joseph, Towia A. Libermann, Carlos Garcia-Echeverria, Mark A. Pearson, Francesco Hofmann, Kenneth C. Anderson Andrew L. Kung: "Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies and solid tumors"

Carlos García-Echeverría, Mark A. Pearson, Andreas Marti, Thomas Meyer, Juergen Mestan, Johann Zimmermann, Jiaping Gao, Josef Brueggen, Hans-Georg Capraro, Robert Cozens, Dean B. Evans, Doriano Fabbro, Pascal Furet, Diana Graus Porta, Janis Liebetanz, Georg Martiny-Baron, Stephan Ruetz, Francesco Hofmann: "In vivo anti-tumour activity of NVP-AEW541 - A novel, potent and selective inhibitor of the IGF-IR kinase"

Published online 26 February 2004; Cancer Cell, Volume 5, Number 3, March 2004.

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

More articles from Health and Medicine:

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

nachricht Highly precise wiring in the Cerebral Cortex
21.09.2017 | Max-Planck-Institut für Hirnforschung

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Party discipline for jumping genes

22.09.2017 | Life Sciences

The pyrenoid is a carbon-fixing liquid droplet

22.09.2017 | Life Sciences

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>