Target Pediatric AML
Together We Can Fund the Cure

Scientific Challenges

Pediatric aml needs to be treated differently


Why are advances lagging in childhood AML – why is the research underfunded and lower priority?

In a nutshell, AML is a rare, diverse, complex, difficult-to-target, “adult” cancer. But, advances in data science and cancer genomics are uncovering new vulnerabilities in AML – essentially providing new “military intelligence” in the war against leukemia. Newly discovered markers, supply lines (drivers and pathways), and other vulnerabilities can be exploited by targeted agents – like modified T-cells. Hope is on the horizon.

A few challenges exist from a scientific perspective:

  • AML is a rare disease, relatively speaking, across all ages and cancers. However, AML is now the leading cause of death from childhood leukemia. Most research funding is directed to the “big killers” like lung and breast cancer, and in pediatrics, to the most common form of childhood leukemia, ALL (acute lymphoblastic leukemia).

  • AML is a complex, diverse GROUP of diseases – not one. Multiple subtypes (and subtypes within subtypes!) exist. One patient’s AML can differ significantly from another’s, so a single “magic bullet” breakthrough is unlikely.

  • Most AML research remains adult-focused because most AML patients are seniors, and due to the lingering belief that we can improve outcomes in childhood AML with “hand-me-down” therapies developed for older adults.

  • Precisely targeting AML – without harming essential, healthy cells – remains a challenge. Creative, combined, and personalized targeting will likely be needed to improve outcomes for everyone.

AML accounts for approximately 21,000 of the 1.7 million cancer diagnoses annually. It is primarily a disease of older adults with a grim prognosis. Since 80% of all cases of AML are diagnosed in patients older than 60, most discovery and biologic data fueling clinical trials have been generated in older adults. It is presumed that discoveries in older adults can be translated to young adults and children simply because their disease shares the same name. This “trickle-down” approach assumes that the biology of AML in young people mirrors older adults. In the past 5 years, the Children’s Oncology Group has demonstrated that, despite morphologic similarity of disease in older and young patients (meaning, the cancer appears similar under a microscope), the disease is entirely different in every possible way, from genetic makeup to response to therapies. The most common mutations driving AML in seniors are simply not found in children, and vice versa. This, combined with the fact that AML remains one of the poorest prognosis pediatric cancers and the leading cause of childhood leukemia-related deaths, underscores that strategic, pediatric-focused AML research is sorely needed.

Another significant challenge in AML is precise targeting, a key reason that T-cell therapies have lagged for this disease. Many currently identified targets for AML also appear on/within normal cells, resulting in challenging toxicities. Identification of more specific, viable targets will be key to maximizing targeted therapies, like modified T-cells, antibody therapies, and small molecule inhibitors. New target discovery one of the primary goals of TpAML.