DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Mantle cell lymphoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMantle cell lymphoma maps to a 46-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
approvedBortezomibApproved drug
Structures already discussed alongside mantle cell lymphoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of the Lon-like protease MtaLonC — Bortezomib has a real, experimentally solved structure in complex with this target (PDB 4FWD, 2.03 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet bo2drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4FWD · 2.03 Å · ligand Bortezomib (BO2). Experimental structure, not a prediction.
What the evidence adds up to
Mantle cell lymphoma is a B-cell lymphoma with a median survival of approximately 5 years and is incurable with standard chemotherapy. A 2004 review states it is the B-cell lymphoma with the worst prognosis and that no standard treatment had resulted in cure. A 2008 review notes that not all patients require therapy at diagnosis. Biological factors conferring poor prognosis include a high-proliferation signature defined by gene expression profiles, loss of p27, and presence of mutant p53. The cell cycle, the ATM gene, and the nuclear factor kappaB pathways are the main targets of genetic abnormalities in the disease.
The best reported results as of 2008 were with rituximab-hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone-methotrexate/cytarabine, but a cooperative group study of this regimen appeared not quite as successful. Consolidation of remission after rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone with high-dose therapy and stem-cell support prolongs remission. A 2004 review states that autologous and allogenic bone marrow transplantations appear to be the only current treatments that might improve outcome. A 2017 review notes that upfront intensive treatment includes autologous stem cell transplantation consolidation aimed at deepening and lengthening remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients in remission features lower-intensity treatments given over extended periods.
Novel agents active in relapsed disease as of 2008 include bortezomib, mammalian target of rapamycin inhibitors, immunomodulatory agents, antibodies, and cyclin pathway-directed agents such as flavopiridol and cyclin-dependent kinase inhibitors. A 2017 review states that the treatment landscape is evolving toward incorporating novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. A 2017 review also highlights a need for personalised therapy to ensure optimal outcomes, but the 2004 review notes that progress in understanding biology had not yet brought any major improvements in therapeutic approaches, which remained highly unsatisfactory. What is still missing is the translation of biological insights into reliably curative regimens, prospective validation of which patients can safely defer therapy, and randomised data showing that any maintenance or targeted strategy meaningfully extends survival rather than just delaying relapse.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2011 · 77 citations · open access
Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma
AbstractBACKGROUND: Bortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations. DESIGN AND METHODS: The activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m² on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m², day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled. RESULTS: The overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy. CONCLUSIONS: Bortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.
Current Opinion in Hematology · 2008 · 42 citations
Mantle cell lymphoma: advances in biology and therapy
AbstractPURPOSE OF REVIEW: Mantle cell lymphoma is characterized by dysregulation of cyclin D1, but this is not sufficient for lymphoma development. It is a difficult disease to treat, being incurable with standard chemotherapy and having a median survival of approximately 5 years. The purpose of this review is to update recent advances in mantle cell lymphoma biology with prognostic and potentially therapeutic implications, and mantle cell lymphoma treatment approaches and new agents. RECENT FINDINGS: Genetic alterations that cooperate with cyclin D1 have been described that alter proliferation, in particular p27Kip and p16INK4, or apoptosis. Biological factors such as high-proliferation signature defined by gene expression profiles, loss of p27 and presence of mutant p53 confer poor prognosis. Proliferative rate also predicts patient outcome. Clinical criteria such as the international prognostic index, follicular lymphoma international prognostic index or a formula using age, performance status, white blood cell count and lactate dehydrogenase, separate prognostic groups. Not all patients require therapy at diagnosis. Although the best reported results have been with rituximab-hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone-methotrexate/cytarabine, a cooperative group study of this regimen appears not quite as successful. Consolidation of remission after rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone with high-dose therapy/stem-cell support prolongs remission and consolidation with radioimmunotherapy shows promise. Intensifying induction by alternating intensified rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone with rituximab and high-dose cytarabine, followed by high-dose therapy appears quite promising. Novel agents active in relapsed disease include bortezomib, mammalian target of rapamycin inhibitors, immunomodulatory agents, antibodies and cyclin pathway-directed agents such as flavopiridol and cyclin-dependent kinase inhibitors. SUMMARY: New insights into mantle cell lymphoma biology may lead to targeted therapy. Meanwhile, combinations of existing therapeutic approaches seem to have improved outcomes.
Current Opinion in Hematology · 2004 · 30 citations
Mantle cell lymphoma
AbstractPURPOSE OF REVIEW: Mantle cell lymphoma is the B-cell lymphoma with the worst prognosis. Until now, no standard treatment has resulted in cure. Improvements in understanding of the disease are needed to advance therapeutic efforts. RECENT FINDINGS: Pathology and immunohistochemistry can identify the subset of patients with the worse prognosis. New data suggest that at least a subset of mantle cell lymphoma cases have undergone some form of antigene selection, and particular types of Ig gene rearrangement seem to give a better prognosis. The cell cycle, the ATM, gene and the nuclear factor kappaB pathways are the main targets of the genetic abnormalities occurring in mantle cell lymphoma: new genomic and expression data have been recently published. Unfortunately, this progress has not yet brought any major improvements in therapeutic approaches, which still remain highly unsatisfactory. Autologous and allogenic bone marrow transplantations appear to be the only current treatments that might improve the outcome of patients with PMCL. New additional treatment modalities are currently under investigation. SUMMARY: This review summarizes all the most recent data published on the biology and treatment of mantle cell lymphoma.
Hematology/Oncology and Stem Cell Therapy · 2017 · 17 citations · open access
Mantle Cell Lymphoma
AbstractMantle cell lymphoma is a clinically heterogeneous disease occurring within a heterogeneous patient population, highlighting a need for personalized therapy to ensure optimal outcomes. It is therefore critical to understand the benefits and risks associated with both intensive and deintensified approaches. In the following review we provide a therapeutic roadmap to strategically guide treatment for newly diagnosed and relapsed/refractory patients highlighting pivotal and recently published results involving known and novel therapies.
Pharmaceuticals · 2017 · 2 citations · open access
Targeted Drugs as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma
AbstractThe treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes. Targeted drugs are a natural fit for this space, and are the focus of considerable clinical investigation. This review summarizes recent advances in the field and their potential impact on treatment practices for MCL.
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.
