DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for childhood acute lymphoblastic leukemia — screening already-approved drugs against its 19-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChildhood acute lymphoblastic leukemia maps to a 19-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for childhood acute lymphoblastic leukemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
gamma-aminobutyric acid type A receptor subunit alpha4 (GABRA4) — GABRA4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet px6drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7QN5 · 2.5 Å · ligand 1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE (PX6). Experimental structure, not a prediction.
What the evidence adds up to
By 1997, around 70 percent of children receiving optimal therapy for acute lymphoblastic leukaemia could expect long-term remission and probable cure, but this required a two-year maintenance phase with methotrexate and other drugs; shorter maintenance led to more relapses, and a minority of patients still relapsed unpredictably within a year or two after stopping chemotherapy. A significant subset of paediatric patients either relapsed or never achieved complete remission, and those identified as high risk by clinical or laboratory findings were unlikely to respond to further minor adjustments of the same chemotherapy drugs. In adult patients, complete remission was achieved in over 90 percent of cases, but sustaining remission remained the challenge, and salvage therapies for relapsed disease offered a poor chance of good outcome.
Many novel targeted therapies for childhood ALL were in varying stages of development by 2010, from clinical trials to preclinical refinement, with the aim of improving cure rates and reducing toxicity to non-malignant cells. By 2019, risk-stratified prospective multicentre studies had further improved survival, and new molecular prognostic factors and tumour subtypes with independent gene expression profiles had been characterised. Therapies targeted to specific candidate mutations were being identified to broaden options for patients with poor prognoses, and immunotherapy was attracting significant interest for recurrent or refractory disease. However, the 2019 review did not report specific response rates or survival figures for these newer approaches.
Earlier work from 1987 had already established that morphologic, immunologic and cytogenetic studies permitted more accurate classification and risk assessment, and that studies of tumour cell biology had begun to pinpoint genes whose altered functions might be linked to leukaemogenesis. A 2013 Mexican research group summarised their experience with molecular epidemiology and proposed a causal model for the origin of childhood ALL, but this was a hypothesis, not a clinical result. Across all these abstracts, no single repurposed drug is named, no concrete response rates or survival numbers are given for any targeted or immunotherapeutic agent, and the adult data confirm that durable remission remains elusive. What is still missing are completed randomised trials that report survival outcomes for the many agents in development, adequate funding to move promising preclinical findings through phase II and III testing, and better patient stratification to identify which children or adults will benefit from which targeted therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 2010 · 38 citations · open access
Targeting paediatric acute lymphoblastic leukaemia: novel therapies currently in development
AbstractModifications to the treatment of acute lymphoblastic leukaemia (ALL) in children have led to a dramatic increase in survival in the past 40 years. Despite this success, a significant subset of paediatric leukaemia patients either relapse or fail to ever achieve a complete remission. Additionally, some patients necessitate treatment with intensified chemotherapy regimens due to clinical or laboratory findings which identify them as high risk. These patients are unlikely to respond to further minor adjustments to the dosing or timing of administration of the same chemotherapy medications. Many novel targeted therapies for the treatment of childhood ALL provide potential mechanisms to further improve cure rates, and provide the possibility of minimizing toxicity to non-malignant cells, given their specificity to malignant cell phenotypes. This article explores many of the potential targeted therapies in varying stages of development, from those currently in clinical trials to those still being refined in the research laboratory.
AbstractRemarkable progress has been achieved in our understanding of the biology of acute lymphoblastic leukemias (ALL) occurring in childhood. Morphologic, immunologic, and cytogenetic studies of ALL have resulted in more accurate classification and risk assessment, permitting tailoring of therapy in this heterogeneous group of diseases. Studies of tumor cell biology have begun to pinpoint genes whose altered functions may be etiologically linked to cancer, and have provided insights into the biochemical processes involved in leukemogenesis.
New England Journal of Medicine · 1997 · 24 citations
Silence of the Leukemic Clone
AbstractThe success of treatment for childhood acute lymphoblastic leukemia (ALL) has been justifiably lauded. Some 70 percent of patients who receive optimal therapy and support can now expect to have a long-term remission and probable cure.1 Most current therapeutic protocols use not only early induction and consolidation phases of combination therapy but also a two-year maintenance phase with methotrexate and other drugs. Clinical trials have clearly demonstrated that this protracted treatment is necessary; a shorter duration of maintenance therapy results in more relapses.2 After the cessation of chemotherapy, a minority of patients unpredictably relapse within a year or two. Overall, . . .
Clinical Epidemiology of Acute Lymphoblastic Leukemia - From the Molecules to the Clinic
AbstractThis book describes different perspectives of childhood acute lymphoblastic leukemia. The approach includes aspects of molecular epidemiology, particularly molecular features that influence the genesis and prognosis of the disease. Some aspects of the prognosis of lymphoblastic leukemias are very detailed, highlighting the use of molecular biology in the early identification of complications that may occur in diseased patients. The authors of the present book conform a Mexican group who identifies the causes of leukemia, and they summarize their experience in research, results and proposals for future studies. A causal model is included in which the authors hypothesized the origin of acute lymphoblastic leukemias, particularly in children. This hypothesis can be useful to better understand other cancers during childhood. This book will help the reader to identify different molecular aspects involved in leukemia, and its relation to the development and evolution of the disease.
Clinical Medicine Insights Oncology · 2012 · 5 citations · open access
Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia
AbstractAcute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hematooncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL.
Imsang soa hyeoraek jong-yang/Imsang soa hyeol'aeg jong'yang/Clinical pediatric hematology-oncology · 2019 · 2 citations · open access
Advances in the Treatment of Childhood Acute Lymphoblastic Leukemia
AbstractIn recent decades, survival rates for childhood acute lymphoblastic leukemia have improved remarkably, as demonstrated by risk-stratified, prospective multicenter studies. Treatment protocols have evolved and become better matched to both prognostic factors and treatment responses. Recently, new molecular prognostic factors have been discovered in leukemia genomic studies. New tumor subtypes with independent gene expression profiles have also been characterized. Furthermore, therapies targeted to specific candidate mutations are being identified to broaden therapeutic options for patients with poor prognoses. Many new drugs are in clinical trials and immunotherapy is attracting significant interest for the treatment of recurrent or refractory disease in childhood acute lymphoblastic leukemia.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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