When It Comes to Cancer, Children Aren’t Little Adults

New research proves that children and adults with cancer often have different mutated genes driving their diseases. This reinforces the need for pediatric-specific precision therapies.

By Maureen Salamon; Photos by Seth Dixon and Ann-Margaret Hedges

Patient Caleb dressed in an adult's clothes

Caleb Brown

Only faulty logic would lead someone to look at a child and merely see a small adult. So why should a child with cancer receive the same medication as an adult with cancer?

New research led by St. Jude Children’s Research Hospital is perfectly poised to transform this way of thinking. Studying a core group of a half-dozen pediatric cancers, scientists showed for the first time that malignancy in children and adults frequently arises from different genes with different mutations.

The results, St. Jude experts contend, should prompt shifts in how new drugs are evaluated. Instead of limiting the study of drugs in children only to those already deemed effective and tolerable in adults—meaning some novel therapies are never tried in pediatric patients—the research hammers home how this prevailing strategy is likely a missed opportunity.

A new resource for clinicians

Overall survival rates for pediatric cancer currently exceed 80%, thanks to treatment advances pioneered at St. Jude and elsewhere. Yet, cancer remains the leading cause of disease-related death among U.S. children ages 1 to 19. The new findings highlight the need to develop targeted medications for pediatric patients and also provide a more accurate roadmap for researchers to accomplish this, says Jinghui Zhang, PhD, St. Jude Computational Biology chair.

Very few drugs are specifically developed for pediatric cancer, because the adult cancer population is much bigger. This information will provide a great resource for researchers and clinicians, giving them the ability to develop new therapies and devise new treatment protocols for children.

Jinghui Zhang, PhD

Jinghui Zhang, PhD

Same diagnoses, different genes: Jinghui Zhang, PhD, St. Jude Computational Biology chair, recently led the most comprehensive study thus far to identify the genetic alterations influencing pediatric cancers.

 

“Very few drugs are specifically developed for pediatric cancer, because the adult cancer population is much bigger,” Zhang explains. “This information will provide a great resource for researchers and clinicians, giving them the ability to develop new therapies and devise new treatment protocols for children.”

Ching-Hon Pui, MD, Oncology chair at St. Jude, vigorously agrees with Zhang.

“All the new drugs are tried in adults first, with few exceptions,” he says. “This is wrong. Just because a drug doesn’t work in adults doesn’t mean it won’t work in children.”

Trinity Cunningham in adult clothes

Trinity Cunningham

Computer crunching on a massive scale

Recently published in the journal Nature, the research by Zhang and her colleagues is the most comprehensive so far to identify the genetic alterations influencing pediatric cancers. Its top finding: Only 45% of the mutated genes driving cancer in children matched the genes driving malignancies in adults.

Conducted in partnership with the National Cancer Institute as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project, the vast effort combined gene sequencing and computer data crunching on a massive scale. Six cancers were spotlighted, including acute lymphoblastic leukemia (ALL), both the B- and T-cell types; acute myeloid leukemia; the bone cancer osteosarcoma; the kidney cancer Wilms tumor; and neuroblastoma, a tumor of the sympathetic nervous system.

The study was especially comprehensive because it implemented three types of gene sequencing on both tumor tissue and normal tissue from 1,699 children and adolescents. These included whole genome sequencing of each person’s entire complement of DNA; exome sequencing of the DNA that encodes cells’ instructions for making proteins; and transcriptome sequencing of genes being expressed in the tumor tissue.

Woods Garrett in adult clothes

Woods Garrett

DNA distinctions come to light

Aside from the startling lack of genetic overlap between adults’ and children’s cancers, Zhang says she was also struck by several other distinctions. About 62% of mutations in pediatric cancer were either “copy-number” alterations—leaving patients with too many or too few copies of particular genes—or gene rearrangements. Conversely, gene changes in adult cancers typically involve what scientists call “point mutations”—only one point, or a few points, of genetic variation, Zhang explains.

An additional surprise was that eight of the 689 pediatric patients with B-cell ALL carried genetic changes previously linked only with skin cancer caused by ultraviolet (UV) radiation. This suggests that exposure to UV light may be a previously unrecognized risk factor for some cases of childhood leukemia. However, this finding needs further experimental confirmation, Zhang notes.

All told, Zhang says these inconsistencies point to another gaping void: Currently, genetic testing in pediatric cancer patients is the same as that done in adults. But these tests shouldn’t be identical.

“The fact that there’s only limited genetic overlap with adult cancer suggests we have to develop genetic testing specifically designed for pediatric cancer,” Zhang says. “This is one of the most important messages we want to address.”

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