Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Bioinformatics Application Designed to Look for New Uses for Old Drug

By BiotechDaily International staff writers
Posted on 18 May 2014
By tying together cancer gene expression patterns with drug activity, scientists have found a possible cancer therapy concealed within an antimicrobial agent.

Developing and evaluating a new anticancer drug can cost a huge amount of money and take many years of research. Finding an effective anti-cancer medication from the pool of drugs already approved for the treatment of other medical disorders could slash a substantial amount of time and money from the process.

Now, using a cutting-edge bioinformatics approach, a team led by investigators from Beth Israel Deaconess Medical Center (BIDMC; Boston, MA, USA) have found that the approved antimicrobial drug pentamidine may help in the treatment of patients with advanced kidney cancer. Described online May 1, 2014, in the journal Molecular Cancer Therapeutics, these new findings reveal how connecting cancer gene expression patterns with drug activity might help advance cancer care.

“The strategy of repurposing drugs that are currently being used for other indications is of significant interest to the medical community as well as the pharmaceutical and biotech industries,” said senior author Towia Libermann, PhD, director of the Genomics, Proteomics, Bioinformatics and Systems Biology Center at BIDMC and associate professor of medicine at Harvard Medical School (Boston, MA, USA). “Our results demonstrate that bioinformatics approaches involving the analysis and matching of cancer and drug gene signatures can indeed help us identify new candidate cancer therapeutics.”

Renal cell cancer consists of multiple subtypes that are likely caused by different genetic mutations. Over the years, Dr. Libermann has been working to identify new disease markers and therapeutic targets through gene expression signatures of renal cell cancer that distinguish these diverse cancer subtypes from each other, as well as from healthy individuals. In this new study, he and his colleagues were searching for agents that might be effective against clear cell renal cancer, the most common and highly malignant subtype of kidney cancer. Even though patients with early stage disease can frequently be effectively treated through surgery, up to 30% of patients with renal cell cancer present with advanced stages of disease at the time of their diagnosis.

To pursue this search, the investigators are using the Connectivity Map (C-MAP) database, a compendium of gene expression data from human cancer cells treated with hundreds of small molecule drugs. “C-MAP uses pattern-matching algorithms to enable investigators to make connections between drugs, genes and diseases through common, but inverse, changes in gene expression,” stated Dr. Libermann. “It provided us with an exciting opportunity to use our renal cell cancer gene signatures and a new bioinformatics strategy to match kidney cancer gene expression profiles from individual patients with gene expression changes inducted by various commonly used drugs.”

After identifying drugs that may reverse the gene expression alterations linked with renal cell cancer, the investigators employed assays to measure the effect of the selected drugs on cells. This led to the identification of a small number of US Food and Drug Administration (FDA)-approved drugs that induced cell death in multiple kidney cancer cell lines. The researchers then assessed three of these drugs in an animal model of renal cell cancer and showed that the antimicrobial agent pentamidine (principally used for the treatment of pneumonia) decreased tumor growth and enhanced survival. Gene expression research using microarrays also identified the genes in renal cell cancer that were counteracted by pentamidine.

“One of the main challenges in treating cancer is the identification of the right drug for the right individual,” clarified first author Luiz Fernando Zerbini, PhD, of the International Center for Genetic Engineering and Biotechnology (Cape Town, South Africa), adding that this bioinformatics application could be an especially valuable lower-cost model in developing countries.

The authors reported that their next phase of the research will be to assess the potential of pentamidine used in combination with the existing standard-of-care therapies to treat kidney cancer. “Since the drugs we are evaluating are already FDA-approved, successful studies in preclinical animal models may enable us to rapidly move these drugs into clinical trials,” added Dr. Libermann.

Related Links:

Beth Israel Deaconess Medical Center
Connectivity Map (C-MAP) database



comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: This novel, flexible film that can react to light is a promising step toward an artificial retina (Photo courtesy of the American Chemical Society).

Novel Nanofilm May Be Artificial Retina Precursor

Researchers have used advanced nanotechnology techniques to develop a light-sensitive film that has potential for future artificial retina applications. Investigators at the Hebrew University of Jerusalem... Read more

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.