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 The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie

nachricht Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New studies increase confidence in NASA's measure of Earth's temperature

A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.

The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

On Mars, sands shift to a different drum

24.05.2019 | Physics and Astronomy

Piedmont Atlanta first in Georgia to offer new minimally invasive treatment for emphysema

24.05.2019 | Medical Engineering

Chemical juggling with three particles

24.05.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>