New child-specific test aims to simplify reports and make them more understandable
Laboratory professionals understand the tsunami of molecular testing. They’ve been exposed to the cresting possibilities found in a greater understanding of disease origin, more precise diagnostics, drug and therapy selections based on gene mutations, risk factors found in a person’s unique biology and the identification of drug targets via newly identified mutations and biomarkers-not forgetting the most important aspect of all: they’ve seen that molecular testing helps to power better patient outcomes.
“Labs ‘get it.’ But treating physicians do not always have training in molecular testing, so there is a degree of confusion and misunderstanding,” said Nazneen Aziz, PhD, when asked about the intersection of molecular testing and pediatric cancer. “Some doctors use testing strategies and treatment protocols that were created back in the ’70s when the only thing we had to offer children with cancer was traditional combined chemotherapy and radiation (COB).”
While COB therapy works to cure tumors in children to an acceptable degree, it also leaves behind an unacceptable legacy of toxicity that follows recipients throughout a lifetime. “It kills cells indiscriminately-anything growing,” said Aziz. “And when you are a child, something is always growing; some system is always developing.” The damage done by COB often shows in adulthood, she explained, in the form of other cancers, other diseases-such as heart disorders, immunological problems, psychological problems, sexual dysfunction and more.
A better option, said Aziz, is to target therapies to specific genes. “Our understanding of cancer biology has led to the realization that most cancers, even those originating from the same organ, are different at the genomic level, and therefore, we have to look at every patient’s cancer at that level to find out what genes are driving the cancer.”
Aziz, a researcher specializing in pediatric genomics, is currently senior vice president of research and chief research officer at Phoenix Children’s Hospital in Arizona. Prior to this position, she was director of molecular medicine at the College of American Pathologists (CAP). In that role, she was responsible for initiating and guiding genomic strategies and projects at CAP and directed the development of the first set of laboratory accreditation standards for clinical tests using next generation sequencing and non-invasive prenatal screening. Aziz also co-authored the American College of Medical Genetics and Genomics guidelines on interpretation of sequence variants.
While genomic testing stands ready to reveal a depth of information about a child’s cancer, physicians are not always well-advised on the best tests to order for young cancer patients. “In fact, pediatric cancers may be due to quite a different set of genes than adult cancers,” Aziz explained.
“There is a frustrating lack of collaboration between doctors and labs. Things happen in the wrong order; doctors send their samples to the lab; and the lab does the tests,” continued Aziz. “But if the lab knew more about the patients before tests were ordered, they could advise physicians on the best available tests for individual patients. We still grapple with confusion by physicians about which way to go.”
Aziz hopes to dispel some of the guesswork for physicians with C3Dx, a laboratory-developed genomic test for unique cancers in children now in the validation phase at Phoenix Children’s Hospital and expected to be available this year.
“This test will look specifically at pediatric cancers by examining a child’s normal exome, cancer exome and RNA through next generation sequencing,” explained Aziz. “It will identify the few mutations that may be causative for the cancer. All of these results will be integrated into a single test report reflecting input from pathologists, geneticists and oncologists. The tumor board discussing this report will also seek input from advisors from the pharmaceutical industry, to pinpoint if there are drugs available and suitable for a child with a specific mutation. There may be nothing actionable for one mutation, and yet, there may be something that does work for another mutation.”
A proponent of translational research-the co-production of knowledge development and clinical practice-Aziz finds promise even in those cases that will be identified as clinically non-actionable.
“As more and more children’s reports are generated, we will be growing a rich source of data to shed light on what the gene variations are and which ones are pathogenic. And if they are non-actionable, we can start working with drug companies to help pinpoint important drug targets. As patients are being tested and [treated], we must use every step in that process to learn a better way to treat the next patient,” she explained.
“Medicine is moving very fast today, and transitions rapidly from bench to bedside” Aziz said. “With this kind of technology and the understanding in patient disease it brings with it, we have to break down silos between research and the clinical world, between labs and doctors. We have a responsibility to transfer knowledge quickly. It takes time to change a culture, but there is no time to waste.”