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

December 16, 2011 in Cancer

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

UB associate professor of , 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 looked for the underlying genetic answers to why some who were treated with anthracylines -- powerful antibiotics like Adriamycin and Daunomycin -- developed cardiomyopathy, such as , later in life.

"Anthracyclines are effective drugs used to treat a variety of pediatric cancers, they are also used to treat 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 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.

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 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 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 ." 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."

Provided by University at Buffalo search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

Small cancer risk following CT scans in childhood and adolescence confirmed

The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...

Cancer created 1 minute ago | popularity not rated yet | comments 0

Changing cancer's environment to halt its spread

By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...

Cancer created 1 hour ago | popularity not rated yet | comments 0

Novel RNA-based classification system for colorectal cancer

A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...

Cancer created 1 hour ago | popularity not rated yet | comments 0

Low radiation scans help identify cancer in earliest stages

A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...

Cancer created 3 hours ago | popularity not rated yet | comments 0

Poliovirus vaccine trial shows early promise for recurrent glioblastoma

An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.

Cancer created 4 hours ago | popularity not rated yet | comments 0


New sleeping pill poised to hit US markets

An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.

Life expectancy gap widens between those with mental illness and general population

The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...

Dietary advice on added sugar is damaging our health, warns heart expert

Dietary advice on added sugar is damaging our health, warns a cardiologist in BMJ today. Dr. Aseem Malhotra believes that "not only has this advice been manipulated by the food industry for profit but it is actually a risk ...

Failure to use linked health records may lead to biased disease estimates

Failure to use linked electronic health records may lead to biased estimates of heart attack incidence and outcome, warn researchers in a paper published in BMJ today.

Iodine deficiency during pregnancy may adversely affect children's mental development

A study of around 1,000 UK mothers and their children, published in The Lancet, has revealed that iodine deficiency in pregnancy may have an adverse effect on children's mental development. The research raises concerns that t ...

Reducing caloric intake delays nerve cell loss

Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...