ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- The ITCC-P4 PDX Platform Enables Preclinical Testing of Pediatric Cancers.Cancer research · 2026Article
- Pre-clinical anti-tumor activity and preliminary safety of METTL3 inhibitors STM2457 and UZH1a in neuroblastoma.Translational cancer research · 2026Article
- Ex vivo drug sensitivity profiling to complement molecular profiling in pediatric precision oncology.NPJ precision oncology · 2026Article
- Advances in multi-omics research on neuroblastoma.Frontiers in pediatrics · 2026Review
- Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology.Annals of medicine and surgery (2012) · 2025Review
- Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA.International journal of molecular sciences · 2025Article
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.Nature communications · 2025Article
- Synergistic drug combination screening using a nanodroplet processing platform to enhance neuroblastoma treatment in TH-MYCN transgenic mice.Bioengineering & translational medicine · 2025Article
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Molecular crosstalk between GPCR and receptor tyrosine-protein kinase in neuroblastoma: molecular mechanism and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.PLoS computational biology · 2024Article
- Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.Nature communications · 2024Article
- ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors.Communications biology · 2023Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. EXPERIMENTAL
designWe compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin, and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX).
resultsLorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX, lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth.
conclusionsIn our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.