Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new approach to faster anticancer drug discovery

14.03.2012
Tracking the genetic pathway of a disease offers a powerful, new approach to drug discovery, according to scientists at the University of California, San Diego School of Medicine who used the approach to uncover a potential treatment for prostate cancer, using a drug currently marketed for congestive heart failure. Their findings are published in the current online issue of the Proceedings of the National Academy of Sciences.

"The science of genomics – the study of all of the genes in a person and how these genes interact with each other and the environment – has revealed many fundamental aspects of biology, including the mechanisms of diseases like cancer. But it has not yet been truly exploited to find new medicines to treat those diseases," said Xiang-Dong Fu, PhD, professor of cellular and molecular medicine and senior author of the PNAS paper.

Fu, with colleagues at UC San Diego and elsewhere, describe a unique screening strategy that compares genes associated with specific disease phenotypes (traits) with small molecules capable of intervening with disease-linked gene-expression events. The high-throughput process, capable of analyzing large numbers of genes and drugs simultaneously, emphasizes investigation of the entire genetic pathway of the disease against a large set of internal controls, rather than its limited phenotype or any particular molecular or cellular target.

Historically, drug discovery has been driven by phenotype- or target-based methodologies.

"For 50 years, the standard phenotype approach emphasized the final outcome without worrying about the mechanism," said Fu. "The process has produced some very good drugs, but researchers often didn't know exactly how or why the drug worked. Aspirin is an example. It's been around for more than a century, but we still don't understand the mechanism in great detail."

More recently, many drug designers have focused upon targeting particular components of a disease, such as a vital molecule or receptor involved in the pathogenic process. The approach has a stronger, more rational scientific basis, said Fu, but remains beset by two fundamental difficulties: "You can create a drug that disrupts a specific disease target, but you also run the risk of causing unforeseen, adverse side effects that might be worse than the disease. Second, there are many places inside of a cell that are essentially 'undruggable.' They are difficult, if not impossible, to intervene with."

The new approach attempts to avoid these problems by emphasizing investigation of the genetic pathways associated with disease processes and how they might be altered to produce a healthful benefit.

"The idea is to identify the genetic troublemakers associated with a disease and then find a way to contain them, not crush them," said Fu. "No gene was ever designed to cause disease. The goal is to find new drugs or ways to convert these genes or the affected cells back to a normal state. In many disease paradigms, you don't want to kill cells. You want to modify them to become healthy again."

While the idea of conducting multi-target screenings is not new, the technology to do so has been limited. Deep sequencing, said Fu, is ideally suited for the purpose.

To illustrate the efficacy of their high-throughput, gene-sequencing approach, Fu and colleagues applied the strategy to prostate cancer, which sometimes becomes resistant to standard antiandrogen hormone therapy. The scientists found that Peruvoside, a cardiac glycoside, strongly inhibits both androgen-sensitive and androgen-resistant prostate cancer cells without triggering severe side effects. Interestingly, a related cardiac glycoside called Digoxin has been used to treat congestive heart failure. A large epidemiological study found protective effects against prostate cancer on patients treated with Digoxin, compared to control cohorts.

"High-throughput genetic sequencing and screening allows you to look deeply into cells and analyze millions of molecules at the same time. The technology is constantly improving and getting cheaper. We think it's a promising strategy for drug discovery," said Fu.

Co-authors include Hairi Li, Dong Wang, Jinsong Qiu, Yu Zhou, UCSD Department of Cellular and Molecular Medicine; Hongyan Zhou and Sheng Ding, Gladstone Institute of Cardiovascular Disease; Xianqiang Li, Signosis, Inc.; and Michael G. Rosenfeld, Howard Hughes Medical Institute, UCSD Department of Medicine.

Funding for this research came, in part, from the Prostate Cancer Foundation and the National Human Genome Research Institute.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>