DeCure for Mature T-cell and NK-cell non-Hodgkin lymphoma
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for mature T-cell and NK-cell non-Hodgkin lymphoma — screening already-approved drugs against its 23-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMature T-cell and NK-cell non-Hodgkin lymphoma maps to a 23-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
approvedDoxorubicinApproved drug
Structures already discussed alongside mature t-cell and nk-cell non-hodgkin lymphoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
dihydrofolate reductase (DHFR) — DHFR is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has nadph dihydro-nicotinamide-adenine-dinucleotide phosphate bound in it, shown as sticks.
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 a retrospective Korean study of 28 patients with mature T/NK-cell lymphoma who received high-dose therapy and autologous stem cell transplantation, the median age was 36 years. Disease status at transplant was initially poor risk in 15 patients, chemosensitive relapse in 8, and chemo-resistant relapse in 5. After high-dose therapy, 20 patients achieved a complete response, including 16 with continued complete response. Two therapy-related deaths occurred. Estimated 3-year event-free survival was 24 months and overall survival was 42 months. Only complete response status after high-dose therapy influenced overall survival. The authors suggest that an initial approach with effective induction and high-dose therapy may result in a better outcome.
Peripheral T-cell lymphomas account for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy has lagged behind that of aggressive B-cell lymphomas, and most peripheral T-cell lymphomas have a poor prognosis. The molecular pathogenesis of most peripheral T-cell lymphomas is poorly understood. Angioimmunoblastic T-cell lymphoma is most likely derived from follicular helper T-cells, a finding that explains many of its pathological and clinical features. NK-cells and T-cells of the innate immune system recognise antigen in the absence of MHC antigens, and lymphomas derived from these cells often involve cutaneous and mucosal sites.
A 2023 narrative review notes that T/NK-cell lymphomas are associated with poorer prognosis and higher treatment toxicity. The review states that international guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for T-cell lymphoma patients, and that a cohesive synthesis of infection outcomes among these patients is lacking. The review outlines recommendations for infection screening, antimicrobial prophylaxis, and vaccination strategies.
New drugs with potential for use in T/NK-cell lymphomas, including monoclonal antibodies, tyrosine kinase inhibitors, synthetic retinoids, immunoconjugates, and immunosuppressive molecules with novel mechanisms of action, were in the early phase of clinical investigation as of 2003. Much remains unknown about the pathogenesis, clinical spectrum, and optimal therapy of T/NK-cell lymphomas. What is still missing are prospective trials large enough to account for the heterogeneity of these lymphomas, reliable biomarkers to stratify patients by risk and likely response, and funding to move early-phase drugs into definitive studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Leukemia & lymphoma/Leukemia and lymphoma · 2005 · 16 citations
High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma
AbstractThe proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.
Recent developments in the biology and therapy of T-cell and natural killer–cell lymphomas
AbstractPURPOSE OF REVIEW: T-cell/natural killer (T/NK)-cell lymphomas represent a group of poor-risk lymphoproliferative disorders that have only recently been recognized as distinct clinicopathologic entities. The average outcome with currently available therapy is substantially inferior to that of aggressive B-cell lymphomas. Significant gaps remain in our knowledge of their origin, diagnosis, and clinical spectrum. This review outlines recent developments in the biology and molecular genetics of these disorders, current diagnostic challenges, and future avenues for therapy. RECENT FINDINGS: Several cancer-prone transgenic mouse models that develop predominantly T/NK-cell lymphomas have been produced in the past 2 to 3 years. These models point to an important role for chronic cytokine stimulation and for disruption of genes involved in the control of chromatin remodeling and maintenance of genome integrity in the pathogenesis of T-cell lymphomas. The recognition of T/NK-cell lymphomas has been greatly facilitated by the broad acceptance of standard diagnostic criteria and by the increasing availability of assays for the analysis of T-cell receptor rearrangement and a more precise definition of functional T/NK-cell subsets. New drugs with potential for use in T/NK-cell lymphomas, including monoclonal antibodies, tyrosine kinase inhibitors, synthetic retinoids, immunoconjugates, and immunosuppressive molecules with novel mechanisms of action are in the early phase of clinical investigation. SUMMARY: Much remains to be learned in the pathogenesis, clinical spectrum, and optimal therapy of T/NK-cell lymphomas. The availability of animal models of disease, new diagnostic tools, and targeted drugs with novel mechanisms of action should lead to rapid progress in this group of malignancies in the near future.
Leukemia & lymphoma/Leukemia and lymphoma · 2023 · 0 citations
Recommendations on prevention of infections in patients with T-cell lymphomas: a narrative review and synthesis
AbstractT/Natural killer (NK) cell lymphomas (TCL) represent a heterogenous subgroup of non-Hodgkin lymphoma, associated with poorer prognosis and higher treatment toxicity. A cohesive synthesis of infection outcomes among TCL patients is lacking. International guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for TCL patients. This systematic narrative review highlights infection outcomes in TCL patients treated with conventional, and novel therapies. Recommendations for infection screening, antimicrobial prophylaxis and vaccination strategies are outined.
State of the Art on T-cell lymphomas: the Pathogenesis
AbstractPeripheral T cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non Hodgkin’s lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities. Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK-cells and T-cells of the innate immune system recognize antigen in the absence of MHC antigens, and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of gd T-cell origin. In contrast most nodal T-cell lymphomas belong to the adaptive immune system. Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (TFH), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts
Refractory NK/T Cell Lymphoma Treated with Bortezomib+Chemotherapy and APBSCT.
AbstractAbstract Abstract 4602 Backgrouds: NK/T cell lymphoma is a rare disease, but usually shows a highly aggressive clinical course and its prognosis is poor due to the stumbling block in early diagnosis and effective management. Until present, there are no consensus treatments especially for recurrent patients. Bortezomib, and other new drugs are subject to active investigation, although only limited preliminary information is available. Here, 3 cases of refractory disseminated NK/T cell lymphoma were treated with Bortezomib plus high dose chemotherapy as salvage therapy. Patients and methods: From 2008–2010, 3 cases of refractory NK/T cell lymphoma, 2 males, 1 female, aged from 26–35, PS 0–1 were enrolled. Former treatments included at least 2–9 months of chemotherapy (CHOP or CHOP like) and local radiotherapy. The stage of patients was III in 2, IV in 1. IPI scores were all in high risk. Result: 3 patients received high dose chemotherapy combined with bortezomib as re-induction treatment. 2 patients received hyperCVAD as induction therapy with bortezomib given 1.3mg/m2 on d2, 5, 9 and 12. 1 patient received bortezomib and SMILE protocol, included bortezomib 1.3 mg/m2 on days1, 4, 8, 11, dexamethasone 20 mg twice a day on days 1 through 4, etoposide 100 mg/m2 on days 1 through 3, ifosphamide 1.0 g/m2 on days 1 through 5, methotrexate 30 mg/m2 on days 4, 11, L-asparaginase 6000U/m2 on days 7, 9, 11, 13, 15. All 3 patients had response to the treatment. HyperCVAD, HDAC+MTX and SMILE protocol combined with bortezomib were also given to the patients as consolidation therapy for 1–4 courses. After 2 course of treatment, 1 patient got CR, 2 got PR. Then ASCT was performed. Condition protocol was SEAM+Bz1.3 mg/m2 on days-4, -1. At a median follow-up for 15 months, the median duration of PFS was 12 months. No PN was found in all patients. SAE were neutropenia and thrombocytopenia grade 4, mucositis grade 3, increase AST grade 2 in 3 patients and HZV infection in 1. Conclusion: Bortezomib combined with high dose therapy may be effective salvage therapy in some refractory disseminated NK/T cell lymphoma, especially in young adults. More cases need to be carefully investigated to explore the effect and side effect in bortezomib plus high dose therapy in this special disease. Disclosures: No relevant conflicts of interest to declare.
Archives of Clinical and Medical Case Reports · 2024 · 0 citations · open access
Outcomes of Gemcitabine, Vinorelbine, and Doxorubicin in Peripheral T-Cell Lymphoma
AbstractPeripheral T-Cell Lymphoma (PTCL) remains a difficult-to-treat heterogeneous group of Non-Hodgkin Lymphomas. Our current treatment guidelines have been largely based on studies evaluating the treatment of B-cell Lymphomas, in which there were small subsets of T-cell lymphoma patients included. Additionally, there is no clear guideline for sequencing of subsequent salvage regimens. Prior retrospective studies have reported activity with the combination chemotherapy, Gemcitabine, Vinorelbine, and Doxorubicin (GVD) in the treatment of relapsed and refractory PTCL, but these have been international retrospective analyses. Thus, we performed a retrospective analysis within our own institution of the efficacy and safety of GVD in the treatment of relapsed and refractory PTCL. We found an overall response rate of 80%, complete response rate of 50%. Complete response rates were higher in patients receiving GVD as second-line therapy as compared to later lines of therapy. GVD was well tolerated with the most common adverse effects being neutropenia, infection, and peripheral neuropathy. Ultimately, our data supports the use of GVD in relapsed and refractory PTCL, with possible greatest benefit when used as second-line therapy.
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.
