DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for acute lymphoblastic leukemia — screening already-approved drugs against its 67-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcute lymphoblastic leukemia maps to a 67-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 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
dihydrofolate reductase (DHFR) — DHFR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
In T-cell acute lymphoblastic leukaemia, the recognition of clinical, genetic, transcriptional and biological heterogeneity has translated into new prognostic biomarkers, improved animal models, and emerging targeted therapies, but no single drug is identified as effective in this 2019 review. Cure rates for paediatric acute lymphoblastic leukaemia exceed 80% in developed countries using protocols with tolerable toxicity, yet in low- and middle-income countries the picture varies; recent advances have improved cure rates there, but problems such as access to care, abandonment of treatment, and protocol toxicity remain critical barriers.
For relapsed or refractory acute lymphoblastic leukaemia, survival remains very low and treatment carries high morbidity. One salvage regimen tested in 29 previously treated adult patients used high-dose cytarabine (3.0 g/m² daily for 5 days) plus a single high dose of idarubicin (40 mg/m² on day 3). Eleven complete responses were observed (38%; 95% confidence interval 20–56%). Four patients subsequently underwent allogeneic bone marrow transplantation. There was one treatment-related death (3%). Two patients with significant prior anthracycline exposure suffered reductions in left ventricular function to the 20–30% range during severe systemic infection; one recovered to 50% after infection resolved. The authors concluded the regimen had moderate activity and a relatively low mortality for this high-risk group.
In adult acute lymphoblastic leukaemia overall, complete remission is achieved in over 90% of patients with induction therapy, but sustained remission remains elusive, and salvage therapies for relapsed disease offer a poor chance of good outcome. Therapeutic strategies including high-dose single agents, intensified induction, new drugs, targeted therapy, and immunotherapy may benefit some patients, but post-remission treatments still need further development. What is missing are adequately powered trials that stratify patients by genetic and clinical risk, sufficient funding to test novel agents in the relapsed setting, and structured implementation of risk-directed therapy and supportive care in low-resource settings.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cold Spring Harbor Perspectives in Medicine · 2019 · 67 citations · open access
The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia
AbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from early T-cell progenitors. The recognition of clinical, genetic, transcriptional, and biological heterogeneity in this disease has already translated into new prognostic biomarkers, improved leukemia animal models, and emerging targeted therapies. This work reviews our current understanding of the molecular mechanisms of T-ALL.
Acute lymphoblastic leukemia in low and middle-income countries
AbstractPURPOSE OF REVIEW: Acute lymphoblastic leukemia is the most common pediatric cancer. The cure rate of this disease is over 80% in developed countries utilizing protocols with very tolerable toxicity. Several factors contributed to this success, including the implementation of large collaborative clinical trials and the better understanding of disease biology allowing for risk-stratified treatment. We will review the current state of the treatment of acute lymphoblastic leukemia in low-income and medium-income countries. RECENT FINDINGS: The picture differs from country to country, but recent advances have been made in many countries and the cure rates have improved significantly. Tackling problems such as access to care, abandonment of treatment and toxicity of protocols and the development of centers of excellence are critical for continued improvement. Twinning with programs in developed countries and the creation of regional collaborative groups will allow the implementation of risk-directed therapy and better supportive care. SUMMARY: The experience in low-income countries shows that a structured approach to the treatment of acute lymphoblastic leukemia results in improved survival.
JCO Oncology Practice · 2022 · 38 citations · open access
Updates in the Management of Relapsed and Refractory Acute Lymphoblastic Leukemia: An Urgent Plea for New Treatments Is Being Answered!
AbstractThe treatment of acute lymphoblastic leukemia (ALL) has dramatically changed over the past three decades. However, relapsed and/or refractory ALL still remains with a very low survival and high morbidity associated with its treatment. Here, we will review the outstanding progress that has been made in the treatment of relapsed and/or refractory ALL and discuss future directions and challenges that require further investigation.
A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia
AbstractBACKGROUND: The majority of adult patients who are treated for lymphoblastic disease will either develop recurrent disease or will be refractory to their initial therapy. One option for patients with recurrent/refractory disease is to administer a reinduction regimen that employs a dose-intense combination of anthracycline and cytarabine. These salvage regimens are relatively distinct from the traditional vincristine/prednisone-based programs that are used typically as primary induction therapy. The authors studied a regimen that contained high-dose cytarabine and a single high dose of idarubicin as salvage induction therapy for patients with recurrent or refractory lymphoblastic disease. METHODS: Twenty-nine previously treated adult patients with recurrent or refractory acute lymphoblastic leukemia were treated with a new intensive regimen. Eight patients had primary refractory disease. Twenty-one patients had recurrent disease, and 16 of these patients developed recurrent disease while they were still receiving their primary therapy. The treatment regimen consisted of cytarabine 3.0 g/m(2) by 3-hour infusion daily for 5 days and idarubicin 40 mg/m(2) given as a single dose on Day 3. Filgrastim (granulocyte-colony stimulating factor) 5 microg/kg administered subcutaneously every 12 hours was started on Day 7 and was continued until the absolute neutrophil count was > 5000/microL. Response was assessed using standard criteria. RESULTS: There were 11 complete responses (38%; 95% confidence interval, 20-56%). Four patients subsequently underwent allogeneic bone marrow transplantation. Moderate but acceptable toxicity was observed given the severely myelosuppressive nature of the regimen. There was only one treatment-related death (3%). Two patients, both with significant prior exposure to anthracyclines, suffered reductions in left ventricular function to the 20-30% range during episodes of severe systemic infection. After recovery from infection, the ejection fraction in one patient improved to 50%. CONCLUSIONS: The authors conclude that this regimen has moderate activity and a relatively low incidence of mortality for this high-risk group of patients. This regimen may be most suitable for patients who can undergo potentially curative allogeneic bone marrow transplantation if they achieve a complete response.
Therapeutic Advances in Hematology · 2013 · 16 citations · open access
Bosutinib in the treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia: an overview
AbstractBosutinib is an orally bioavailable SRC/ABL tyrosine kinase inhibitor with activity against all phases of resistant chronic myeloid leukemia that do not express the T315I or V299L ABL kinase domain mutations. Bosutinib has a unique toxicity profile that is manageable. This paper provides an overview of bosutinib, covering pharmacodynamics and pharmacokinetic properties, results of treatment in newly diagnosed and previously treated chronic myeloid leukemia patients, as well as common side effects.
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.
The Journal of Pediatric Pharmacology and Therapeutics · 2020 · 5 citations · open access
Pharmacokinetics, Efficacy and Safety of Bosutinib in a Pediatric Patient With Chronic Myeloid Leukemia
AbstractBosutinib is a second-generation tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia (CML) in adult patients. The safety and efficacy of bosutinib in patients younger than 18 years of age have not been established. We here report the case of a 4-year-old male with CML who was treated with bosutinib during coordination of human leukocyte antigen–matched unrelated bone-marrow transplantation because of insufficient responses to imatinib and dasatinib. The patient achieved a complete cytogenetic response immediately after starting bosutinib at 180 mg/day (290 mg/m 2 /day). Because toxicity was tolerable, the dose was increased to 200 mg/day (330 mg/m 2 /day). A complete cytogenetic response was maintained, but a major molecular response was not achieved 6 months after initiation of treatment with bosutinib. At steady state, maximum plasma concentration, minimum plasma concentration, and area under the plasma concentration-time curve were 89.2 ng/mL, 16.7 ng/mL, and 1017.4 ng·hr/mL, respectively, at 290 mg/m 2 /day; and 141.1 ng/mL, 18.9 ng/mL, and 1278.5 ng·hr/mL, respectively, at 330 mg/m 2 /day. To the best of our knowledge, this is the first case report to show the pharmacokinetics of bosutinib with efficacy and safety in a pediatric patient with CML. This rare case in a very young child with CML can also be valuable reference for clinical practice.
Chemotherapy strategies in adult refractory/relapsed acute lymphoblastic leukemia
AbstractThe treatment for adult refractory /relapsed acute lymphoblastic leukemia is a major challenge in clinical practice. Therapeutic strategies including high-dose single agent,intensified induction,new drugs,targeted therapy,and immunotherapy etc. may be of benefit to some patients. The post-remission treatments remain to be further developed.
Key words:
Leukemia,lymphocytic,acute; Adult; Refractory/recurrence; Antineoplastic combined chemotherapy protocols
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
