Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Childhood cancer drugs cure now, may cause problems later, UB research shows

19.12.2011
Study indicates that drug toxicity may be related to genetic factors

Will a drug used to treat childhood acute lymphoblastic leukemia and other pediatric cancers cause heart problems later in life?

UB associate professor of pharmaceutical sciences, Javier G. Blanco, PhD, who sees his work as a bridge between research and clinical practice, has focused recent efforts on trying to answer this question.

Blanco and colleagues' recent study in the Journal of Clinical Oncology looked for the underlying genetic answers to why some childhood cancer survivors who were treated with anthracylines -- powerful antibiotics like Adriamycin and Daunomycin -- developed cardiomyopathy, such as congestive heart failure, later in life.

"Anthracyclines are effective drugs used to treat a variety of pediatric cancers, they are also used to treat breast cancer and other malignancies in adults," Blanco says. "After cancer, survivors can develop cardiac toxicity anywhere from one year to more than 15 years after the initial chemotherapy with anthracyclines. The window separating the effectiveness of these drugs from their toxicity is narrow. The dosage has to be precise to achieve a therapeutic effect without toxicity."

Blanco explains that the key to individualizing any drug treatment comes down to understanding the way an individual is genetically coded to respond to the drug once it enters the body, and then adjusting the dose accordingly.

A photo of Blanco is available here: http://www.buffalo.edu/news/13076.

Working closely with Smita Bhatia, MD, MPH, chair of the Department of Population Sciences at City of Hope National Medical Center in California and senior author of the study, Blanco and a team of researchers decided to look at how the drug was broken down by enzymes encoded by specific genes.

The study, which began seven years ago, compared DNA genotypes of 170 childhood cancer survivors diagnosed with anthracycline-related cardiomyopathy to a control group of 317 survivors without heart disease.

Using the candidate gene approach, Blanco and his team were able to identify a tiny gene variant related to the risk of cardiotoxicity.

"We pinpointed the genetic difference or polymorphism that makes an enzyme work faster or slower in patients," said Blanco, "slower is better."

They zeroed-in on carbonyl reductases (CBR1 and CBR3) -- two enzymes that break down anthracyclines into cardiotoxic alcohol metabolites. Blanco notes that in mouse models, higher levels of CBRs or faster enzymes dictate higher levels of these metabolites -- and more cardio toxicity.

The research showed that the risk of cardiomyopathy was significantly increased among individuals with two copies of the "G" version of the CBR3 polymorphism when exposed to low-to-moderate doses of anthracycline.

Blanco says that while the results of the study validated the findings of an earlier study in a totally independent cohort of cancer survivors, further study is required.

"We have to be careful," says Blanco. "So far, we are showing an association, not yet causation. Our next step will be to conduct a prospective study -- where we don't study individuals who were exposed to anthracyclines in the past but follow them in real time as they are receiving the drug and after."

What does this mean for children who are taking or have taken anthracyclines?

"If we stop using anthracyclines we will not be able to cure up to 90 percent of the children who suffer from acute lymphoblastic leukemia." Blanco says. "Parents must continue to have their children's health monitored long after the cancer is cured to identify cardiac problems if they develop."

Blanco's research is primarily funded by the National Institute of General Medical Sciences (NIGMS), the Lance Armstrong Foundation and the Leukemia and Lymphoma Society, among many others.

The Children's Oncology Group (COG), whose mission is to eradicate childhood cancer, issued the study report. COG also provided the group of researchers Blanco collaborated with and helped to provide the study's subjects. The COG unites more than 7,500 experts in over 200 children's hospitals, universities and cancer centers. Blanco has been a member of the COG since 2001.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

Sara Saldi | EurekAlert!
Further information:
http://www.buffalo.edu

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>