DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Mast Cell Neoplasm — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMast Cell Neoplasm maps to a 15-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
approvedDasatinibApproved drugapprovedNilotinibApproved drug
Structures already discussed alongside mast cell neoplasm 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 EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 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 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
Systemic mastocytosis is now understood as a clonal neoplastic disorder of a haematopoietic progenitor cell, driven in many cases by activating codon 816 mutations of the c-kit gene. That mutation has also been used as a tracking marker to demonstrate clonality. The recognition that pathological mast cell growth depends on Kit signalling has led to interest in drugs that target the mutated Kit protein, but no such targeted agent is described in these abstracts.
Two infants with solitary mastocytoma were treated with oral tranilast at 5 mg/kg/day, a mast cell stabilising compound extracted from Nandina domestica. One infant also received a topical corticosteroid. The nodules resolved almost completely after eight weeks, and no relapses were seen after six months of therapy. The authors speculated that tranilast might reduce mast cell numbers, not merely inhibit degranulation. No larger or more recent trial of tranilast in mastocytosis is reported here.
A separate immunohistochemical study of mast cell tryptase in 20 cases of oral leukoplakia, 20 cases of oral squamous cell carcinoma, and 10 normal gingival samples found a progressive increase in mean mast cell count: 7.73 in normal mucosa, 15.11 in leukoplakia, and 22.73 in carcinoma. The intergroup differences were statistically significant (p = 0.001). The authors concluded that mast cells favour malignant transformation and can serve as indicators of disease progression, but this study concerns oral carcinogenesis, not mast cell neoplasms.
A retrospective study of 62 dogs with cutaneous mast cell tumours treated by surgical resection at a single veterinary hospital found that low-grade tumours were associated with lower rates of ulceration, metastasis, recurrence, and paraneoplastic syndrome, and less need for adjuvant therapy, compared with high-grade tumours. High-grade tumours had greater metastatic potential, and the presence of neoplastic cells in adjacent tissues was linked to more postoperative complications. No human drug trial data are provided.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Acta Haematologica · 2005 · 53 citations
Clonality and Molecular Pathogenesis of Mastocytosis
AbstractMast cell is a hematopoietic lineage dependent on Kit signaling for growth, differentiation, and survival. Mast cells are found in excessive numbers in tissues in a heterogeneous group of disorders collectively known as mastocytosis. Last decade has witnessed important advancements in our understanding of the molecular pathology of mastocytosis. First, systemic mastocytosis has been found to be associated with activating codon 816 mutations of the c-kit gene. Second, this mutation was used as a tracking marker to elucidate the clonal nature of mastocytosis. These findings have resulted in consideration of systemic mastocytosis as a clonal neoplastic disorder of a hematopoietic progenitor cell. Improved knowledge of the mechanisms causing pathological mast cell growth will lead to the discovery of novel treatment options including drugs targeting the mutated Kit protein.
A Phase II Study of Nilotinib, a Novel Inhibitor of c-Kit, PDGFR, and Bcr-Abl, Administered to Patients with Systemic Mastocytosis.
AbstractAbstract Systemic mastocytosis is a clonal disorder associated with a constitutive activation of the c-kit tyrosine kinase based on point mutations and is characterized by mast cell infiltration of extracutaneous organs. Nilotinib is a novel aminopyrimidine which potently inhibits Bcr-Abl, as well as the PDGF-R, and c-kit tyrosine kinases. Preclinical data demonstrated the activity of nilotinib against D816V mutated c-kit in biochemical and cellular assays. This Phase II study was designed to evaluate the safety and efficacy of nilotinib administered at an oral dose of 400 mg twice daily to patients with systemic mastocytosis defined by specific disease criteria and with a clinical indication for treatment. Data are available for 60 patients (34 male, 26 female). The median age is 51 years (range, 29 to 79). Of the 60 patients 31 (52%) had extramedullary involvement at baseline. In 30/36 patients investigated (83%) D816V c-kit mutation was found by D-HPLC and/or conventional sequencing in bone marrow or extracutaneous organs. Two patients showed the c-kit I798I polymorphism. Treatment is ongoing for 38 (63%) patients; 22 (37%) have discontinued; ten (17%) for adverse events, seven (12%) withdrew consent, and one (2%) each for disease progression and lost to follow-up. There were two (3%) deaths related to disease progression. Based on investigators’ assessment of serum tryptase, bone marrow mast cell counts and improvement of clinical symptoms 12 patients (20%) had a documented clinical response including two (3%) complete, five (8%) incomplete, four (7%) minor, and one partial response. Adverse events occurring in >15% of patients included nausea in 28 (47%), headache in 26 (43%), fatigue in 25 (42%), vomiting in 22 (37%), diarrhea in 21 (35%), pruritis in 16 (27%), and rash in 15 (25%) patients, dizziness and muscle spasms in 14 (23%) patients each, bone pain in 12 (20%), pyrexia and myalgias in 11 (18%) patients each, and dyspnea, constipation, increased ALAT, and arthralgias in ten (17%) patients each. Most side effects occurred early after initiation of nilotinib therapy and were successfully treated with H1- and H2-blockers and/or corticosteroids, indicating a mast cell degranulation syndrome. Overall the most frequent Grade 3/4 adverse events included diarrhea in four (7%) patients, and thrombocytopenia and headache in three (5%) patients each. The data suggest that nilotinib has clinical activity and an acceptable safety and tolerability profile in patients with systemic mastocytosis with constitutive c-kit activation. Individual molecular characterization will help to guide targeted therapy in this disease.
AbstractTwo infants with solitary mastocytoma were treated with 5 mg/kg/day of tranilast [N-(3',4'-dimethoxycinnamoyl)anthranilic acid], a mast cell stabilizing compound extracted from Nandina domestica. Tranilast was administered orally in three divided doses. In one infant, a topical corticosteroid was also applied in combination with the oral tranilast. Patients experienced symptomatic relief, and nodules resolved almost completely after eight weeks of treatment. Tranilast therapy was continued for six months. No relapses were observed after discontinuation of therapy. We speculated that tranilast not only inhibited mast cell degranulation but also reduced the number of mast cells.
Response to Dasatinib in Patients with Aggressive Systemic Mastocytosis with D816V Kit Mutation.
AbstractAbstract Human systemic mastocytosis (SM) is a rare disease caused by an abnormal mast cells accumulation in various tissues. It usually occurs as a sporadic disease that is often persistent or progressive in adults. Clinical course is variable. The most aggressive forms have a rapid course and required treatments to reduce the neoplastic burden and to slacken the progression. Unfortunately no therapy have been demonstrated efficacy, mostly in the treatment of aggressive systemic mastocytosis (ASM). SM has been associated with constitutive activating c-kit somatic mutations, the most frequent of whom is the D816V mutation. Kinase inhibitors blocking constitutive c-kit activation, such as imatinib, have been used in SM, but they had no effect on D816V mutant kit. Here, we report on six patients with Systemic mastocytosis and with detectable D816V mutation treated with dasatinib 70 mg BID as in leukemia treatment. According to the WHO Classification of Systemic mastocytosis, we describe clinical characteristics of six cases of ASM with different organ damage treated with dasatinib for various period, and we made evaluation of response according to Valent criteria (Leuk Research, 2003). All patients excepting Patient 3 reached the dose of 140 mg daily. Patient 4 are on treatment after 10 months, without any signs or symptoms of disease progression. Patient 2 is still on treatment with low dose of dasatinib (20 mg daily) but he shows cytopenia and worsening clinical condition, he does not tolerate high dose of dasatinib for gastrointestinal toxicity and astenia. Patient 1 stopped therapy after 10 months of therapy and she relapsed with ascite and died after 1 month for progressive disease. Patient 3 and Patient 5 interrupted dasatinib for worsening clinical condition after 40 days and three months respectively. Patient 6 stopped dasatinib after five months for progression to acute leukemia. After dasatinib suspension, Patient 3 died for complication of leg fracture and Patient 5 died for progression of disease. We observed major response in three patients for the prompt resolution of sign of organ damage recorded during dasatinib treatment, and we also obteined a measurable decrease of the burden of neoplastic MCs by means of tryptase level monitoring in all but one patients. Toxicity of 140 mg daily in patients with advanced ASM is notable. All patients had to suspended therapy due to extra-haematological toxicity. The most commonly toxicity involved gastroenteric tract, with diarrohea and abdominal pain, hypotension and pleural effusion. Symptoms resolved or return to mild grade with dose reduction, but in frail patients therapy is not well tolerate. After interruption of therapy progression was recorded.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2016 · 6 citations · open access
Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma
AbstractINTRODUCTION: More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. AIM: The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. MATERIALS AND METHODS: Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. RESULTS: The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. CONCLUSION: Mast cells favour malignant transformation and can be used as indicators of disease progression.
Prognostic factors and complications attributed to surgical resection of cutaneous mast cell tumors in 62 dogs attended in UNESP-Jaboticabal veterinary hospital from 2013 to 2019
AbstractMast cell tumors, which are neoplasms with variable behavior, from less aggressive to highly metastatic tumors, account for 16%–21% of cutaneous neoplasms in dogs. The diagnosis and grading of mast cell tumors are based on cytological analysis and histological evaluation, which facilitate appropriate planning for surgical and chemotherapeutic treatment. Surgical resection with safety margins of 2–3 cm is considered the best therapeutic option; however, postoperative complications, such as delayed healing, necrosis, suture dehiscence, and occurrence of seroma, are reported. It is essential to understand the biology of mast cell tumors because prognostic factors directly influence the efficacy of the treatment and the quality of life of the patient. Here, we conducted a retrospective study of dogs submitted to surgical resection of cutaneous mast cell tumors, and analyzed the prognostic factors and occurrence of postoperative complications. The results showed that low grade mast cell tumors were associated with a lower occurrence of ulceration, metastasis, recurrence, lack of need for adjuvant therapy, and occurrence of paraneoplastic syndrome compared to those of a higher grade. We also compared the association between demanding or compromised margins with the presence of postoperative complications. The results showed that high grade mast cell tumors have a greater metastatic potential and that the presence of neoplastic cells in the adjacent tissues leads to a greater malignancy and postoperative complications.
Clinical Atlas of Canine and Feline Ophthalmic Disease · 2015 · 0 citations
Mast Cell Tumor (MCT)
AbstractThis chapter presents an overview of Mast cell tumors (MCTs) which are relatively common eyelid neoplasms. Lesions typically present as progressive, firm, raised masses, which may or may not ulcerate. Local extension into surrounding tissues may occur. Commonly affected breeds include the Boston Terrier, Labrador Retriever, and Boxer. The diagnosis of MCT is based on representative tissue biopsy. Histopathology will confirm the diagnosis, as well as degree of malignancy of neoplasia present. Presurgical treatment using an antihistamine or corticosteroid is considered appropriate in view of the potential for neoplastic degranulation in association with manipulation. The potential for metastasis exists and staging via local lymph node aspiration, three-view radiography, and complete blood count (CBC)/chemistry analysis is recommended. Management options include wide surgical excision (where possible), local treatment with strontium, and/or external-beam (electron) radiation where appropriate.
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.
