{"entity":{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","aka":[],"tldr":"Children's cancers were made curable by decades of cooperative trials that refined chemotherapy dose by dose. The next gains come from immunotherapy and targeted drugs built for children's cancers, from laws that stop companies skipping children, and from protecting the child who is cured from the cost of the cure.","summary":"Childhood leukaemia was fatal in 1948 and is curable today because cooperative groups in North America and Europe ran one randomised trial after another, each refining the previous regimen. The same method made neuroblastoma, Wilms tumour, Ewing sarcoma and medulloblastoma curable in most children, and the Childhood Cancer Survivor Study then documented what those cures cost decades later: heart damage, second cancers, infertility and hearing loss.\n\nThe present era brought engineered immunity to children first. Blinatumomab, the first T-cell engager, and tisagenlecleucel, the first CAR-T ever approved (2017, after ELIANA), both started in childhood leukaemia; anti-GD2 antibodies raised cure rates in high-risk neuroblastoma. Precision medicine followed: Pediatric MATCH screened children nationally for targetable mutations, and paediatric-first drugs arrived for the commonest childhood brain tumour (tovorafenib) and for diffuse midline glioma (dordaviprone). The RACE for Children Act, in force since 2020, requires companies to study new targeted cancer drugs in children whenever the target matters in a childhood cancer, and the ACCELERATE platform brings companies, regulators and parents together to plan those studies.\n\nThe pace is set by the smallness of the market, which no incentive fully corrects; by regulatory divergence between the FDA and EMA; by late effects that are still under-recorded; and by the fact that most children with cancer live in countries where cure rates are a fraction of those in rich ones.","asOf":"2026-09-10","links":[{"label":"ACCELERATE Paediatric Strategy Forums","url":"https://www.accelerate-platform.org/paediatric-strategy-forums/"},{"label":"Childhood Cancer Survivor Study","url":"https://ccss.stjude.org"},{"label":"WHO Global Initiative for Childhood Cancer","url":"https://www.who.int/initiatives/the-global-initiative-for-childhood-cancer"}],"tags":[],"related":["alexs-lemonade-stand","st-baldricks","idea-bio2-paediatric-first-development","idea-tr2-paediatric-combo-prea","idea-reg-single-paediatric-plan","idea-reg-orphan-designation-reciprocity","idea-fund-amc-paediatric-rare","idea-fund-paediatric-deferral-escrow","idea-data-paediatric-rwe-consortium","idea-acc-childhood-medicines-platform-scale","idea-acc-abandonment-stipends","idea-acc-paediatric-palliative-in-every-childhood-unit","idea-gd2-car-t-frontline-consolidation","idea-bio1-fusion-tf-degraders","idea-mfbg-pet-replaces-mibg","idea-moon-hearing-protection-cisplatin","cell-therapy-roadmap","survivorship-roadmap"],"cancers":["neuroblastoma","dipg-dmg","paediatric-low-grade-glioma","all-leukemia"],"sections":[],"technologies":["car-t","tandem-transplant","mibg-theranostics","glioma-car-t","fertility-preservation","survivorship-care-plan","cgp","pdx-models"],"targets":[],"drugs":["methotrexate","vincristine","mercaptopurine","asparaginase","dinutuximab","i131-mibg","blinatumomab","tisagenlecleucel","tovorafenib","dabrafenib-trametinib","selumetinib","larotrectinib","dordaviprone","vorasidenib","sodium-thiosulfate","dexrazoxane","mifamurtide"],"companies":["childrens-oncology-group","itcc","day-one-biopharmaceuticals","y-mabs"],"institutions":["siop-europe","accelerate-platform","st-jude","fda-oce","ema"],"pathways":[],"terms":["race-for-children-act","orphan-drug","accelerated-approval"],"trials":["int-0091","hr-nbl1","anbl0032","anbl0532","anbl1531","aren0533","acns0331","euramos-1","interfant-06","aaml0531","inter-b-nhl-ritux-2010","ccss","tower","eliana","aall1731","gd2-cart01","pediatric-match","firefly-1","tadpole","action-dmg"],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment","b-regulatory-fragmentation","b-survivorship","b-global-access","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1948-1990s","title":"Cooperative groups make childhood cancer curable","description":"Methotrexate produced the first remissions of childhood leukaemia in 1948; St Jude's Total Therapy and the cooperative groups that became the Children's Oncology Group and SIOP Europe turned remission into cure by combining vincristine, mercaptopurine, asparaginase and methotrexate and testing every change against the last regimen. INT-0091 set the Ewing sarcoma backbone; tandem transplant and busulfan-melphalan (HR-NBL1) defined high-risk neuroblastoma therapy. Almost every child in a rich country was enrolled in a trial, which is why progress was so fast.","refs":["methotrexate","vincristine","mercaptopurine","asparaginase","st-jude","childrens-oncology-group","siop-europe","int-0091","tandem-transplant","anbl0532","hr-nbl1","interfant-06"],"status":"historic"},{"era":"1994-2015","title":"Immunotherapy for neuroblastoma, and counting the cost of cure","description":"The anti-GD2 antibody dinutuximab raised cure rates in high-risk neuroblastoma (ANBL0032) and was approved in 2015; radioactive MIBG treated the tumour from inside. Risk-adapted trials gave less to children who needed less: AREN0533 in Wilms tumour, ACNS0331 in medulloblastoma. The Childhood Cancer Survivor Study, following tens of thousands of survivors from 1994, showed the late effects of anthracyclines, radiation and alkylators and produced the long-term follow-up guidelines every survivor clinic uses.","refs":["dinutuximab","anbl0032","y-mabs","i131-mibg","mibg-theranostics","aren0533","acns0331","euramos-1","mifamurtide","aaml0531","inter-b-nhl-ritux-2010","ccss","survivorship-care-plan"],"status":"historic"},{"era":"2014-2026","title":"Engineered immunity, children first","description":"Blinatumomab, the first T-cell engager (2014), nearly doubled survival in relapsed leukaemia (TOWER) and then, added to standard treatment for average-risk childhood leukaemia (AALL1731), pushed cure rates higher still. Tisagenlecleucel became the first CAR-T ever approved, in 2017, after ELIANA put most children whose leukaemia had returned after every standard treatment into remission. GD2 CAR-T produced durable complete remissions in neuroblastoma (GD2-CART01) and is being taken into the brain for diffuse midline glioma.","refs":["blinatumomab","tower","aall1731","tisagenlecleucel","eliana","car-t","gd2-cart01","idea-gd2-car-t-frontline-consolidation","glioma-car-t","cell-therapy-roadmap"],"status":"current"},{"era":"2017-2026","title":"Precision medicine and the regulatory lever","description":"Pediatric MATCH (from 2017) screened children with relapsed cancer nationally and assigned them to targeted drugs by mutation, with ITCC's ESMART as its European counterpart. The RACE for Children Act, in force for applications from August 2020, ended the exemption that let companies skip children when the drug's target matters in a childhood cancer; the ACCELERATE platform, founded in 2013, convenes companies, the FDA, the EMA and parents to decide which drugs to study and how. Paediatric-first drugs followed: tovorafenib for BRAF-driven low-grade glioma (FIREFLY-1), dabrafenib-trametinib beating chemotherapy in the same disease (TADPOLE), selumetinib for neurofibromatosis, and dordaviprone, the first drug for diffuse midline glioma. ACTION is the first placebo-controlled phase 3 ever run in that disease.","refs":["pediatric-match","itcc","cgp","race-for-children-act","accelerate-platform","fda-oce","ema","tovorafenib","firefly-1","day-one-biopharmaceuticals","tadpole","dabrafenib-trametinib","selumetinib","larotrectinib","dordaviprone","action-dmg","vorasidenib"],"status":"current"},{"era":"2016-2026","title":"Protecting the child who is cured","description":"Sodium thiosulfate, an old antidote, halves permanent hearing loss from cisplatin in two paediatric trials and is now standard; dexrazoxane protects the heart from anthracyclines; fertility preservation is offered before gonadotoxic treatment; risk-based survivorship follow-up is organised from the CCSS evidence. Adults are only now getting the otoprotection children have, a reversal of the usual direction of travel.","refs":["sodium-thiosulfate","idea-moon-hearing-protection-cisplatin","dexrazoxane","fertility-preservation","ccss","survivorship-care-plan","survivorship-roadmap"],"status":"current"},{"era":"2026-2030","title":"Next trials, next targets, one global plan","description":"ANBL1531 adds targeted radiation and immunotherapy into neuroblastoma induction; CAR-T for brain tumours is in early trials; degraders for the fusion transcription factors that drive childhood sarcomas are the first credible attack on those drivers. The regulatory proposals: develop drugs in children first when the target is a children's target, make paediatric combination studies part of every relevant adult approval, one global paediatric development plan instead of separate FDA and EMA plans, and automatic reciprocity of orphan designations. A same-day PET tracer could replace two-day MIBG scans.","refs":["anbl1531","glioma-car-t","idea-bio1-fusion-tf-degraders","idea-bio2-paediatric-first-development","idea-tr2-paediatric-combo-prea","idea-reg-single-paediatric-plan","idea-reg-orphan-designation-reciprocity","idea-mfbg-pet-replaces-mibg","pdx-models"],"status":"emerging"},{"era":"2030+","title":"Every child, everywhere","description":"Most children with cancer live in countries where cure rates are a fraction of those in rich ones, and where families abandon curative treatment because they cannot afford transport and food. Guaranteed-quality childhood cancer medicines free of charge in fifty countries, cash stipends to prevent abandonment, a paediatric palliative team in every childhood unit, and an international consortium pooling the outcome of every treated child are the proposals. Advance market commitments and escrowed adult revenue would pay for the drugs no market will.","refs":["idea-acc-childhood-medicines-platform-scale","idea-acc-abandonment-stipends","idea-acc-paediatric-palliative-in-every-childhood-unit","idea-data-paediatric-rwe-consortium","idea-fund-amc-paediatric-rare","idea-fund-paediatric-deferral-escrow","st-jude","alexs-lemonade-stand","st-baldricks"],"status":"speculative"},{"era":"What sets the pace","title":"Markets, regulators, late effects and geography","description":"Each childhood cancer is too small a market for a company to pursue, and orphan incentives only partly correct that. The FDA and EMA require different paediatric plans, so studies are duplicated or delayed. Late effects are recorded in cohorts, not in routine care. And the children who most need the cures already found live where they are not available. Charities and cooperative groups fill the gap that the market leaves.","refs":["b-rare-cancers","b-incentive-misalignment","b-regulatory-fragmentation","b-survivorship","b-global-access","b-trial-enrolment","orphan-drug","accelerated-approval"],"status":"current"}],"watch":[]},"route":"/roadmaps/paediatric-oncology-roadmap/","neighbours":{"collection":[{"id":"alexs-lemonade-stand","kind":"collection","name":"Alex's Lemonade Stand Foundation (ALSF)","route":"/collections/alexs-lemonade-stand/"},{"id":"st-baldricks","kind":"collection","name":"St. Baldrick's Foundation","route":"/collections/st-baldricks/"}],"idea":[{"id":"idea-mfbg-pet-replaces-mibg","kind":"idea","name":"18F-MFBG PET replacing 123I-MIBG scintigraphy","route":"/ideas/idea-mfbg-pet-replaces-mibg/"},{"id":"idea-acc-paediatric-palliative-in-every-childhood-unit","kind":"idea","name":"A paediatric palliative care team in every childhood cancer unit","route":"/ideas/idea-acc-paediatric-palliative-in-every-childhood-unit/"},{"id":"idea-fund-amc-paediatric-rare","kind":"idea","name":"Advance market commitments for paediatric and rare cancer drugs","route":"/ideas/idea-fund-amc-paediatric-rare/"},{"id":"idea-data-paediatric-rwe-consortium","kind":"idea","name":"An international consortium pooling the outcome of every treated child with cancer","route":"/ideas/idea-data-paediatric-rwe-consortium/"},{"id":"idea-reg-orphan-designation-reciprocity","kind":"idea","name":"Automatic reciprocity of orphan and rare-paediatric designations between regulators","route":"/ideas/idea-reg-orphan-designation-reciprocity/"},{"id":"idea-acc-abandonment-stipends","kind":"idea","name":"Cash for transport and food to stop families abandoning curative treatment","route":"/ideas/idea-acc-abandonment-stipends/"},{"id":"idea-bio1-fusion-tf-degraders","kind":"idea","name":"Degraders for the fusion proteins that drive childhood sarcomas","route":"/ideas/idea-bio1-fusion-tf-degraders/"},{"id":"idea-bio2-paediatric-first-development","kind":"idea","name":"Develop drugs in children first when the target is a children's target","route":"/ideas/idea-bio2-paediatric-first-development/"},{"id":"idea-fund-paediatric-deferral-escrow","kind":"idea","name":"Escrow a share of adult revenue until the paediatric study is done","route":"/ideas/idea-fund-paediatric-deferral-escrow/"},{"id":"idea-gd2-car-t-frontline-consolidation","kind":"idea","name":"GD2 CAR-T as consolidation in high-risk neuroblastoma","route":"/ideas/idea-gd2-car-t-frontline-consolidation/"},{"id":"idea-acc-childhood-medicines-platform-scale","kind":"idea","name":"Guaranteed-quality childhood cancer medicines free of charge in 50 countries","route":"/ideas/idea-acc-childhood-medicines-platform-scale/"},{"id":"idea-tr2-paediatric-combo-prea","kind":"idea","name":"Make paediatric combination studies part of every relevant adult cancer drug approval","route":"/ideas/idea-tr2-paediatric-combo-prea/"},{"id":"idea-reg-single-paediatric-plan","kind":"idea","name":"One global paediatric cancer development plan instead of separate FDA and EMA plans","route":"/ideas/idea-reg-single-paediatric-plan/"},{"id":"idea-moon-hearing-protection-cisplatin","kind":"idea","name":"Protect hearing from cisplatin in adults as we now do in children","route":"/ideas/idea-moon-hearing-protection-cisplatin/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"},{"id":"rejuvenation-roadmap","kind":"roadmap","name":"Recovery and rejuvenation roadmap: cure is not enough → survivorship gets a name → the cohorts that measured the cost → exercise proven as treatment → biological ageing measured and sold → repair, if anyone funds it","route":"/roadmaps/rejuvenation-roadmap/"},{"id":"survivorship-roadmap","kind":"roadmap","name":"Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards","route":"/roadmaps/survivorship-roadmap/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"wilms-tumor","kind":"cancer","name":"Wilms tumour (nephroblastoma)","route":"/cancers/wilms-tumor/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"glioma-car-t","kind":"technology","name":"CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)","route":"/technologies/glioma-car-t/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"rejuv-paed-late-mortality","kind":"technology","name":"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked","route":"/technologies/rejuv-paed-late-mortality/"},{"id":"mibg-theranostics","kind":"technology","name":"MIBG imaging and 131I-MIBG therapy","route":"/technologies/mibg-theranostics/"},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","route":"/technologies/fertility-preservation/"},{"id":"pdx-models","kind":"technology","name":"Patient-derived xenografts","route":"/technologies/pdx-models/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"},{"id":"tandem-transplant","kind":"technology","name":"Tandem autologous transplant","route":"/technologies/tandem-transplant/"}],"drug":[{"id":"i131-mibg","kind":"drug","name":"131I-MIBG (iobenguane I-131) therapy","route":"/drugs/i131-mibg/"},{"id":"asparaginase","kind":"drug","name":"Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)","route":"/drugs/asparaginase/"},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"dexrazoxane","kind":"drug","name":"Dexrazoxane","route":"/drugs/dexrazoxane/"},{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"},{"id":"dordaviprone","kind":"drug","name":"Dordaviprone","route":"/drugs/dordaviprone/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"mercaptopurine","kind":"drug","name":"Mercaptopurine","route":"/drugs/mercaptopurine/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"mifamurtide","kind":"drug","name":"Mifamurtide","route":"/drugs/mifamurtide/"},{"id":"selumetinib","kind":"drug","name":"Selumetinib","route":"/drugs/selumetinib/"},{"id":"sodium-thiosulfate","kind":"drug","name":"Sodium thiosulfate (otoprotectant)","route":"/drugs/sodium-thiosulfate/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"},{"id":"tovorafenib","kind":"drug","name":"Tovorafenib","route":"/drugs/tovorafenib/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"},{"id":"vorasidenib","kind":"drug","name":"Vorasidenib","route":"/drugs/vorasidenib/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"},{"id":"day-one-biopharmaceuticals","kind":"company","name":"Day One Biopharmaceuticals","route":"/companies/day-one-biopharmaceuticals/"},{"id":"itcc","kind":"company","name":"Innovative Therapies for Children with Cancer (ITCC)","route":"/companies/itcc/"},{"id":"y-mabs","kind":"company","name":"Y-mAbs Therapeutics","route":"/companies/y-mabs/"}],"institution":[{"id":"accelerate-platform","kind":"institution","name":"ACCELERATE","route":"/institutions/accelerate-platform/"},{"id":"ema","kind":"institution","name":"European Medicines Agency","route":"/institutions/ema/"},{"id":"fda-oce","kind":"institution","name":"FDA Oncology Center of Excellence","route":"/institutions/fda-oce/"},{"id":"siop-europe","kind":"institution","name":"SIOP Europe (European Society for Paediatric Oncology)","route":"/institutions/siop-europe/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"term":[{"id":"accelerated-approval","kind":"term","name":"Accelerated approval","route":"/terms/accelerated-approval/"},{"id":"orphan-drug","kind":"term","name":"Orphan drug","route":"/terms/orphan-drug/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"}],"trial":[{"id":"action-dmg","kind":"trial","name":"ACTION","route":"/trials/action-dmg/"},{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"},{"id":"aall1731","kind":"trial","name":"COG AALL1731","route":"/trials/aall1731/"},{"id":"aaml0531","kind":"trial","name":"COG AAML0531","route":"/trials/aaml0531/"},{"id":"acns0331","kind":"trial","name":"COG ACNS0331","route":"/trials/acns0331/"},{"id":"anbl0032","kind":"trial","name":"COG ANBL0032","route":"/trials/anbl0032/"},{"id":"anbl0532","kind":"trial","name":"COG ANBL0532","route":"/trials/anbl0532/"},{"id":"anbl1531","kind":"trial","name":"COG ANBL1531","route":"/trials/anbl1531/"},{"id":"aren0533","kind":"trial","name":"COG AREN0533","route":"/trials/aren0533/"},{"id":"eliana","kind":"trial","name":"ELIANA","route":"/trials/eliana/"},{"id":"euramos-1","kind":"trial","name":"EURAMOS-1","route":"/trials/euramos-1/"},{"id":"firefly-1","kind":"trial","name":"FIREFLY-1","route":"/trials/firefly-1/"},{"id":"gd2-cart01","kind":"trial","name":"GD2-CART01 (Bambino Gesù phase 1/2)","route":"/trials/gd2-cart01/"},{"id":"int-0091","kind":"trial","name":"INT-0091 (Ewing sarcoma)","route":"/trials/int-0091/"},{"id":"inter-b-nhl-ritux-2010","kind":"trial","name":"Inter-B-NHL Ritux 2010","route":"/trials/inter-b-nhl-ritux-2010/"},{"id":"interfant-06","kind":"trial","name":"Interfant-06","route":"/trials/interfant-06/"},{"id":"pediatric-match","kind":"trial","name":"NCI-COG Pediatric MATCH (APEC1621)","route":"/trials/pediatric-match/"},{"id":"hr-nbl1","kind":"trial","name":"SIOPEN HR-NBL1","route":"/trials/hr-nbl1/"},{"id":"tadpole","kind":"trial","name":"TADPOLE (CDRB436G2201)","route":"/trials/tadpole/"},{"id":"tower","kind":"trial","name":"TOWER","route":"/trials/tower/"}],"bottleneck":[{"id":"b-incentive-misalignment","kind":"bottleneck","name":"Incentives reward me-too drugs and marginal gains","route":"/bottlenecks/b-incentive-misalignment/"},{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-regulatory-fragmentation","kind":"bottleneck","name":"Regulatory divergence between regions","route":"/bottlenecks/b-regulatory-fragmentation/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"}]}}