DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for DICER1-related tumor predisposition — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDICER1-related tumor predisposition maps to a 1-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 dicer1-related tumor predisposition 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
dicer 1, ribonuclease III (DICER1) — DICER1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7XW2 · 3.04 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
DICER1 syndrome is a rare genetic disorder caused by germline mutations in the DICER1 gene and predisposes to both benign and malignant tumours. One case report describes a prepubertal girl who developed ovarian Sertoli-Leydig cell tumour, thyroid follicular carcinoma, embryonal rhabdomyosarcoma of the cervix, and a lung cyst; genetic analysis confirmed a mutation in the 14q32.13 locus. The authors emphasise the need for early diagnosis and close follow-up for DICER1-related pathologies, as well as genetic evaluation of the family.
A 2025 report on two children with DICER1-associated sarcomas that had relapsed or progressed after upfront multimodal therapy found that both tumours carried cooperating mutations in HRAS or BRAF. One child was treated with dabrafenib and trametinib, but the mutant BRAF became amplified, presumably driving acquired resistance. In the second case, a subclonal HRAS variant at diagnosis became the predominant clone at autopsy, suggesting its role in therapy resistance. The authors conclude that these cases provide molecular evidence of the importance of RAS/ERK signalling in DICER1-driven tumourigenesis but do not report any durable response or survival benefit from targeting these mutations.
A review of Dicer’s role in human pathologies notes that germline mutations are linked to DICER1 syndrome, but states that the exact correlation of Dicer protein expression across different cancer types is unclear and that there are contradictions in the data. Downregulation of Dicer is associated with geographic atrophy, depression, and Parkinson’s disease, while both loss and upregulation are implicated in autoimmune disorders including psoriasis, rheumatoid arthritis, and multiple sclerosis. Loss of Dicer also contributes to cardiovascular disease and reproductive abnormalities.
A 2022 analysis of DICER1 mutations in the TCGA database across ten cancer types found that DICER1 mutation was associated with better clinical outcomes in pan-cancer and specifically in uterine corpus endometrial carcinoma. The authors suggest that DICER1 mutation may facilitate antitumour immunity and could be a potential biomarker for immunotherapy, but they note that more clinical and basic research is needed to validate this. What remains missing are prospective clinical trials that stratify patients by DICER1 mutation status, standardised treatment protocols for the rare sarcomas that arise in this syndrome, and funding to support the multi-centre collaboration necessary to study such a small patient population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Molecular Sciences · 2020 · 41 citations · open access
Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies
AbstractGene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson’s disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.
RAS pathway targeted therapy in patients with DICER1-associated sarcomas
AbstractDICER1-associated sarcomas commonly exhibit cooperating mutations involving RAS signaling pathways, but the efficacy of therapies that target these mutations is unknown. Here we report two children with DICER1 tumor predisposition who presented with DICER1-associated sarcomas with cooperating, targetable mutations in HRAS or BRAF. Both had relapsed/progressed disease despite upfront multimodal therapy and were subsequently treated with molecularly targeted agents. In the first case, mutant BRAF became amplified after dual dabrafenib/trametinib therapy, presumably as a driver of acquired resistance. In the second case, a subclonal HRAS variant at diagnosis became the predominant clone at autopsy, suggesting its importance in therapy resistance. Together, these two cases provide molecular evidence of the significance of RAS/ERK signaling in DICER1-driven tumorigenesis and highlight the potential for targeting these cooperating mutations.
The Turkish Journal of Pediatrics · 2021 · 2 citations · open access
Sertoli-Leydig cell tumor, thyroid follicular carcinoma and rhabdomyosarcoma of the uterine cervix in a prepubertal girl with pathogenic germline variant in DICER1 gene
AbstractBACKGROUND: DICER1 syndrome is a hereditary cancer predisposition syndrome which is related DICER1 gene and may present a variety of manifestations. CASE: A prepubertal girl with ovarian Sertoli-Leydig cell tumor, thyroid follicular carcinoma, embryonal rhabdomyosarcoma of the cervix and lung cyst is presented. Genetic analysis demonstrated mutation (c.3377delC, c.71delC) in 14q32.13 loci and confirmed the diagnosis of DICER1 syndrome. CONCLUSION: The case is presented to emphasize the importance of early diagnosis of alterations in DICER1 gene and close follow-up for the development of DICER1 syndrome related pathologies, and necessity for genetic evaluation of the family.
Research Square · 2022 · 0 citations · open access
A Potential Prognosis and Immune Biomarker in Cancer: DICER1
AbstractAbstract Background: DICER1 plays a significantly important role in short dsRNA-mediated post-transcriptional gene silencing that is deeply embedded in the network of cancer genes. Aberrant expression and mutation of DICER1 have been studied and reported to be closely associated with tumorigenesis and development, while lower levels of DICER1 mRNA or protein are associated with poorer prognosis in some cancers. However, there is little research about the effect and mechanism of mutated DICER1. Materials and Methods: In our study, DICER1 mutation in the TCGA database from the top 10 cancers were analyzed to explore the effect of DICER1 mutants in cancer prognosis and the possible potential mechanisms. Results: We found that DICER1 mutation was closely related to better clinical outcomes in pan-cancer and uterine corpus endometrial carcinoma (UCEC) treatment, which meant that DICER1 could be served as a prognosis factor for pan-cancer, especially UCEC. And mechanism research indicated that DICER1-mut facilitated antitumor immunity, which could be the potential mechanism for DICER1-mut prognosis value. Moreover, tumor microenvironment (TME) features and higher TMB of DICER1-mut manifested that DICER1 may be a potential biomarker of immunotherapy, which needed more clinical and basic research to validate. Conclusions: In summary, our finding suggested that DICER1 may be a potential prognostic biomarker and was associated with TME in UCEC. In addition, it might be a marker of immunotherapy.
Sage Journals Data · 2021 · 0 citations · open access
sj-xlsx-1-tmj-10.1177_03008916211058788 – Supplemental material for Clinical heterogeneity and reduced penetrance in DICER1 syndrome: a report of three families
AbstractSupplemental material, sj-xlsx-1-tmj-10.1177_03008916211058788 for Clinical heterogeneity and reduced penetrance in DICER1 syndrome: a report of three families by Jacopo Azzollini, Andrea Ferrari, Alessandra Stracuzzi, Stefano Chiaravalli, Monica Terenziani, Filippo Spreafico, Maurizia Grasso, Paola Collini, Valeria Pensotti, Maura Massimino, Eloisa Arbustini and Siranoush Manoukian in Tumori Journal
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.
