Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting bone metastasis and hypercalcemia

19.11.2002


Most cancer patients are not killed by their primary tumors but succumb to metastatic disease. The most common human cancers--lung, breast, and prostate--frequently spread to bone, causing suffering and morbidity through pain, fractures, and nerve compression syndromes.



Tumor cells enter bones through blood and lymphatic vessels. In order to establish bone metastases, they have to influence bone metabolism. Most breast cancers that spread to bone express high levels of parathyroid hormone related protein, or PTHrP, a molecule that promotes bone breakdown. Scientists believe that the bone breakdown caused by PTHrP starts a vicious cycle: cross-talk between the tumor cells and the osteoclasts, cells that specialize in breaking down bone, ultimately leads to more and more bone loss and more and more aggressive growth of the tumor.

Consistent with this scenario, inhibition of osteoclast activity not only decreases bone lesions but also reduces tumor burden in animals. Preliminary results from human patients treated with bisphosphonates, a group of drugs also used to prevent and treat osteoporosis, suggest that the same might be true in humans.


An article in the November 18 issue of the Journal of Clinical Investigation focuses on direct inhibition of PTHrP, the molecule that is believed to play a critical role in starting the vicious cycle in most breast cancers that metastasize to bone.

Wolfgang Gallwitz and colleagues (of Osteoscreen Ltd in San Antonio, Texas) identified two compounds that inhibit PTHrP production in human breast cancer cells. In animal models, the compounds did reduce metastatic bone breakdown, and compared favorably with bisphoshonates. The mode of action of the two classes of drugs is different--the new compounds inhibit PTHrP production and secretion by the tumor cells whereas bisphosphonates inhibit osteoclasts--which suggests that the two drugs might have synergistic effects when used in combination.

In an accompanying Commentary, T. John Martin, of St. Vincent’s Institute of Medical Research in Melbourne, Australia, discusses the findings in the context of our understanding of bone metabolism and comments on potential therapeutic benefits and risks of PTHrP inhibitors in cancer.

PTHrP secretion by tumor cells frequently causes another complication in cancer patients, namely elevated calcium levels. The excess calcium comes on the one hand from increased breakdown of bone, and on the other from increased retention of calcium by the kidney. Hypercalcemia occurs in an estimated 10-20% of cancer patients and is the most common life-threatening metabolic abnormality associated with neoplastic disease. Mouse studies performed by Gallwitz and colleagues suggest that their PTHrP inhibitors have potential in the treatment of hypercalcemia as well.


CONTACT:
Wolfgang E. Gallwitz
OsteoScreen, Inc.
Suite 201
2040 Babcock Road
San Antonio, TX 78229
USA
Phone 1: 210-614-0770
Fax 1: 210-614-0797
E-mail: gallwitz@osteoscreen.com


ACCOMPANYING COMMENTARY:
Manipulating the environment of cancer cells in bone: a novel therapeutic approach

CONTACT:
T. John Martin
St. Vincent’s Institute of Medical Research
9 Princes Street
Fitzroy, Melbourne, Victoria 3065
AUSTRALIA
PHONE: 61-3-9288-2480
FAX: 61-3-9416-2676

E-mail: j.martin@medicine.unimelb.edu.au




Brooke Grindlinger, PhD | EurekAlert!
Further information:
http://www.jci.org/
http://www.the-jci.org/press/17124.pdf
http://www.the-jci.org/press/11936.pdf

More articles from Health and Medicine:

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>