Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

Bioinformatics Application Designed to Look for New Uses for Old Drug

By BiotechDaily International staff writers
Posted on 18 May 2014
ADVERTISEMENT
SARTORIUS AG
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



Channels

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.