Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New drugs, new ways to target androgens in prostate cancer therapy

21.06.2012
Prostate cancer cells require androgens including testosterone to grow. A recent review in the British Journal of Urology International describes new classes of drugs that target androgens in novel ways, providing alternatives to the traditional methods that frequently carry high side effects.
“In many ways, therapies for prostate cancer have led the way in the fight against the disease,” says E. David Crawford, MD, investigator at the University of Colorado Cancer Center and review co-author. “The first effective oral therapy for any cancer was estrogen which was described in 1941. The first cancer biomarker that allowed diagnosis and staging was prostatic acid phosphatase back in 1938. Then there was little progress for over four decades.”

During those 40 years, in which early work in prostate cancer led to Nobel prizes for researchers Charles Huggins and Andrew Schally, other cancer types capitalized on this research, notably developing hormone therapies targeting estrogen in breast cancer. But work in prostate cancer stalled.

“What we realized is that production of androgens like testosterone depends on an intact system in which the brain recognizes hormone levels, signals the pituitary to increase or decrease production, and the pituitary in turn sets the testes in motion. Additionally, by targeting the production of androgens by the testes, we could break that system at many other points,” Crawford says.

For example, estrogen is similar enough to testosterone that administering estrogen to patients tricked the brain into thinking testosterone hormone levels were high – with high presumed hormone levels, the brain sent no production signal to the pituitary. But estrogen therapy led to side effects including breast enlargement.

The next class of drugs, known as luteinizing hormone releasing hormones or LHRHs, intervened in this signaling chain at the level of the pituitary. Just as estrogen keeps the brain from signaling for more testosterone, LHRHs keep the pituitary from passing messages to the testes.

“Because the effects of LHRHs are reversible, this allowed us to use hormone-targeting therapies much earlier in the disease,” Crawford says. “But LHRHs lead to an initial spike in testosterone, before it decreases.” Most patients can withstand this spike, but for some, for example those with bone metastasis in the back, a spike in testosterone could flare the disease and lead to spinal complications.

“It was only about ten years ago that somebody was able to make a usable antagonist,” Crawford says. Instead of first spiking and then lowering testosterone, these LHRH antagonists lead to an immediate drop.

And instead of targeting the signaling pathway that leads to the production of androgens including testosterone, androgen antagonists like Enzalutamide (formerly known as MDV3100), currently in phase III clinical trials, target cells’ ability to trap testosterone that exists in the body – it doesn’t matter how much testosterone is floating around, as long as prostate cancer cells are unable to grab it. Specifically, Enzalutamide and other androgen antagonists are easier to “catch” than the androgens themselves, and so cells grab Enzalutamide and are then unable to grab testosterone.

Also new to the field are drugs that block the production of androgens from all sources which of course includes the testes, but also includes blocking the smaller amounts produced by the adrenals and even by the cancer itself. This class of drugs is called androgen biosynthesis inhibitors, and the first approved is a drug called abiraterone or Zytiga.

“Targeting cells’ androgen receptors is a new and exciting development in the field of prostate cancer therapy,” Crawford says. “As these new drugs make their way from the lab to clinic, we expect the ability to offer androgen antagonists to patients whose cancers have resisted other treatments.”

Dr. Crawford wishes to disclose that he is an advisor to the company Medivation, which manufactures the drug Enzolutamide.

Erika Matich | EurekAlert!
Further information:
http://www.ucdenver.edu

More articles from Health and Medicine:

nachricht Vanishing capillaries
23.03.2017 | Technische Universität München

nachricht How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego

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: 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

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>