Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first

The 1948 antifolate that produced the first chemotherapy remissions in childhood leukaemia and the first cure of a solid tumour; still essential in ALL, lymphoma, osteosarcoma and CNS lymphoma.

A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.

Mercaptopurine is a daily tablet, or a liquid for children, that keeps acute lymphoblastic leukaemia in remission during the long maintenance phase of treatment.

An enzyme that starves leukaemia cells of an amino acid they cannot make; a mainstay of childhood ALL therapy for 50 years, with new versions solving allergy and supply problems.

The only NCI comprehensive cancer centre devoted to children, where Total Therapy protocols made childhood leukaemia curable; families are never billed for care.

The Children's Oncology Group is the world's largest paediatric cancer trials organisation; most children with cancer in North America are treated on or according to a COG protocol.

The European paediatric oncology society and the umbrella for the European clinical trial groups that treat most children with cancer on shared protocols.

Adding ifosfamide and etoposide improved cure rates for localised Ewing sarcoma, setting the backbone still used today.

Two rounds of very high-dose chemotherapy with stem-cell rescue, back to back, used in high-risk neuroblastoma in North America.

COG ANBL0532 showed that two transplants in a row beat one in high-risk neuroblastoma.

Europe's long-running high-risk neuroblastoma trial set busulfan-melphalan as the transplant regimen and showed that adding IL-2 to anti-GD2 therapy added toxicity but not benefit.

The largest infant leukaemia trial showed that intensifying chemotherapy did not help, and set the stage for adding blinatumomab instead.

The antibody that raised cure rates in high-risk childhood neuroblastoma by about 20 points when given after transplant with immune boosters and retinoid.

The trial that made anti-GD2 immunotherapy standard for children with high-risk neuroblastoma, improving survival by about 20 points.

MSK spin-out that commercialises naxitamab, the humanised anti-GD2 antibody for relapsed neuroblastoma, and develops pretargeted radioimmunotherapy.

High-dose radioactive MIBG delivers radiation from inside neuroblastoma cells that take up noradrenaline; used for relapsed disease and tested in upfront therapy.

A noradrenaline look-alike that neuroblastoma cells swallow: labelled with a small amount of radioactivity it shows the tumour on a scan; with a large amount it treats it.

A risk-adapted Wilms tumour trial: children whose lung metastases vanished after six weeks of chemotherapy were spared lung radiation, while those with stubborn nodules or a high-risk chromosome pattern got stronger chemotherapy and did better than in the past.

This trial asked whether children with average-risk medulloblastoma could safely receive less radiation. Shrinking the boost to the tumour bed was safe; cutting the dose to the whole brain and spine in young children was not, so 23.4 Gy remains the floor for most.

The largest osteosarcoma trial ever run, across four cooperative groups on two continents. Neither adding interferon for good responders nor adding ifosfamide and etoposide for poor responders improved outcomes, so three-drug MAP chemotherapy remained the standard and the field turned to new biology.

An immune-activating drug approved in Europe for osteosarcoma after a trial suggested it improved survival; the FDA never approved it, and it remains one of oncology's transatlantic disagreements.

Adding the antibody-drug conjugate gemtuzumab ozogamicin to chemotherapy lowered the chance of relapse in children with acute myeloid leukaemia. Years after the drug had been withdrawn from the US market, this trial helped bring it back for children.

Adding the antibody rituximab to intensive chemotherapy in children with high-risk Burkitt and related lymphomas cut treatment failures by about two-thirds, making an already curable disease more so. It is the model of a joint European-North American children's cancer trial.

The largest study of what happens to children after cancer is cured. Following tens of thousands of survivors for decades, it showed that heart damage, second cancers and other late effects were common after older treatments, and that gentler modern protocols have already halved late deaths.

Organised follow-up for the 18 million US and 50+ million global cancer survivors: watching for recurrence and second cancers, managing long-term side effects such as heart damage, infertility, neuropathy and fatigue, and helping people return to work and life.

Blinatumomab was the first T-cell engager (2014), and is now given to children and adults with leukaemia even when in remission, because it improves survival.

The first randomised proof that a T-cell engager beats chemotherapy: blinatumomab nearly doubled survival in relapsed adult ALL.

In children with average-risk leukaemia, adding blinatumomab pushed three-year disease-free survival from 88% to 96%, one of the largest gains in decades.

Tisagenlecleucel was the first CAR-T therapy ever approved (2017), for children and young adults whose leukaemia had come back after everything else.

ELIANA was the global trial behind the first CAR-T approval: four in five children with no options left went into remission, and many stayed there for years.

A patient's T cells are removed, given a synthetic receptor that recognises the cancer, multiplied, and put back as a living drug.

GD2-CART01 was the first CAR-T to produce durable complete remissions in a childhood solid tumour: two-thirds responded and a third achieved complete remission.

Give engineered GD2 T cells to children in remission after standard therapy, where the long-term data show the deepest and longest cures.

Engineered immune cells delivered directly into the brain or spinal fluid. Some children with diffuse midline glioma, a brainstem tumour with no curative treatment, have had striking, if temporary, responses.

From a cure for some leukaemias in 2017 to the first solid-tumour CAR-T and the prospect of making CAR-T inside the body with an injection.

Pediatric MATCH was the first nationwide precision-medicine trial for children: every child with a relapsed solid tumour could have their tumour sequenced and, if a matching drug existed, join a trial arm for it. It proved the plumbing works, even though most single drugs given alone did little.

Europe's network of children's hospitals that run the first trials of new cancer drugs in children, so that European children can access experimental medicines close to home.

Sequencing hundreds of cancer genes at once from a biopsy to find the mutations a drug can target.

A US law that makes drug companies test new targeted cancer drugs in children whenever the drug's target matters in a childhood cancer, instead of letting them skip children because their cancers are rare.

A Brussels-based forum where children's cancer doctors, drug companies, regulators and parents agree how new cancer drugs should be tested in children, so that fewer promising medicines skip childhood cancers.

The US regulator's oncology hub, which approves cancer drugs, runs accelerated approval and Project Orbis, and is pushing better dose-finding through Project Optimus.

The EU agency whose Committee for Medicinal Products for Human Use recommends the marketing authorisations for cancer drugs across all member states.

Tovorafenib is a pill for the most common childhood brain tumour, low-grade glioma driven by BRAF changes, approved in 2024.

FIREFLY-1 showed that a once-weekly pill, tovorafenib, shrinks most relapsed childhood low-grade gliomas driven by BRAF changes, including the common KIAA1549-BRAF fusion that older BRAF drugs could not treat safely. It led to the first approval of a drug for this disease.

Paediatric-first oncology company whose tovorafenib became the first targeted therapy for childhood low-grade glioma.

The first randomised trial to show that a targeted drug pair beats chemotherapy in children with a brain tumour. Children whose low-grade glioma carries a BRAF V600 mutation had far more tumour shrinkage and a much longer time before progression on dabrafenib plus trametinib than on standard carboplatin and vincristine.

Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.

Selumetinib (Koselugo) is the first medicine for children and adults with neurofibromatosis type 1 whose plexiform neurofibromas, benign but disfiguring and painful nerve tumours, cannot be removed by surgery.

The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.

Dordaviprone is the first drug ever approved for a lethal childhood and young-adult brain tumour, diffuse midline glioma with the H3 K27M mutation (August 2025).

ACTION is the first placebo-controlled phase 3 trial ever run in diffuse midline glioma, the childhood brain-stem tumour that radiotherapy alone has never cured. It asks whether taking dordaviprone after radiotherapy lengthens life.

The first targeted therapy for low-grade brain tumours, delaying the need for radiation and chemotherapy by years.

An old antidote proven in two paediatric trials to halve permanent hearing loss from cisplatin, and approved in 2022 as the first drug to prevent a chemotherapy side effect in children.

Cisplatin causes permanent hearing loss. A cheap drug, sodium thiosulfate, protects children; test and roll it out for adults too.

Dexrazoxane protects the heart from the cumulative damage of doxorubicin in women with metastatic breast cancer who need to keep receiving it, and, as Totect, limits tissue destruction when an anthracycline leaks out of a vein.

Protecting the ability to have children before cancer treatment that damages eggs, sperm or the womb: sperm and egg or embryo freezing, ovarian tissue freezing, ovarian shielding and, for some breast cancers, temporary ovarian suppression.

The largest study of what happens to children after cancer is cured. Following tens of thousands of survivors for decades, it showed that heart damage, second cancers and other late effects were common after older treatments, and that gentler modern protocols have already halved late deaths.

Organised follow-up for the 18 million US and 50+ million global cancer survivors: watching for recurrence and second cancers, managing long-term side effects such as heart damage, infertility, neuropathy and fatigue, and helping people return to work and life.

Supportive care began as the drugs that let people get through chemotherapy. It is now a discipline with randomised proof that exercise, early palliative care and symptom monitoring lengthen life, and its next task is organised lifelong care for the growing population of people living after cancer.

COG ANBL1531 is the current North American high-risk trial, adding targeted radiation during induction and an ALK pill for children whose tumours carry ALK mutations.

Engineered immune cells delivered directly into the brain or spinal fluid. Some children with diffuse midline glioma, a brainstem tumour with no curative treatment, have had striking, if temporary, responses.

Some sarcomas in children are caused by two genes fused into one abnormal protein. That protein is the whole disease, but no drug binds it. Destroying it instead of blocking it could work.

Children wait years for drugs because adult trials come first, even when the target belongs to a childhood cancer. Some drugs should start with children.

Children's cancers are treated with combinations, but companies study new drugs in children one at a time. Approvals should require the combination study children actually need.

Companies must agree separate plans for testing new cancer drugs in children with US and European regulators. A single agreed plan would get children access sooner.

A rare cancer drug designated 'orphan' in the US must reapply in Europe, Japan and elsewhere. Recognising each other's decisions would save small companies months.

A same-day PET tracer could replace the two-day, low-resolution MIBG scan children now undergo repeatedly.

A patient-derived xenograft is a patient's tumour grown in a mouse, used to test drugs before they reach people.

Most children with cancer in rich countries are cured; most in poor countries are not, often because cheap drugs are missing. A global platform now ships quality drugs free; scaling it to 50 countries would be one of the highest-value cancer interventions available.

Many children and adults in poorer countries stop curable cancer treatment because families cannot afford the bus fare or food while in hospital. Small, reliable payments during treatment prevent this.

Children with cancer, and their families, need symptom relief and support from diagnosis, not only at the end. Every children's cancer unit should have a palliative team, and most in poorer countries have none.

Childhood cancers are rare, so no one country sees enough cases. Pool the treatment and outcome of every child treated anywhere into one governed dataset.

Payers would promise in advance to buy a set number of doses at a set price for any drug that meets a defined bar in a rare or childhood cancer, so companies know the market exists before they invest.

Companies often delay the childhood cancer studies they are required to do. A slice of the adult drug's revenue would be held back until the paediatric trial is completed.

The only NCI comprehensive cancer centre devoted to children, where Total Therapy protocols made childhood leukaemia curable; families are never billed for care.

A childhood-cancer charity started by a four-year-old patient's lemonade stand that now funds hundreds of grants and runs an open-science data lab for paediatric cancer genomics.

A head-shaving fundraiser that became the largest charitable funder of children's cancer research in the US, underwriting much of the cooperative-group trial infrastructure that treats most American children with cancer.

Taken together rare cancers are a fifth of all cancers, but each one alone is too small for a company to invest in.

The system pays the same for a drug that adds two months as for a cure, so companies race to copy rather than to cure.

Regulatory divergence means a drug approved in one country can take years to reach another, or never arrive.

Tens of millions of people live after cancer with heart damage, infertility, second cancers and fear, and few services.

Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce.

Fewer than one in ten adults with cancer joins a trial. Trials close for lack of patients, not lack of ideas.

A drug for a rare disease (in the US, fewer than 200,000 patients) that gets extra incentives, tax credits, fee waivers and seven years of market exclusivity, to make development worthwhile. Most cancers qualify, so most cancer drugs are orphans.

FDA approval based on early evidence (like tumour shrinkage) on condition that a confirmatory trial follows.