DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for sebaceous adenocarcinoma — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSebaceous adenocarcinoma maps to a 42-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 sebaceous adenocarcinoma 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
isocitrate dehydrogenase (NADP(+)) 2 (IDH2) — IDH2 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 5I96 · 1.55 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Sebaceous carcinoma is an uncommon but aggressive cutaneous malignancy, and the evidence base for systemic therapy is essentially absent. A 2020 review reports a 5-year overall survival rate of 78% for localised or regional disease and 50% for metastatic disease, with incidence rising in the United States for unclear reasons. A retrospective series of 31 ocular adnexal cases from 1984 to 2006 found tumour-related deaths in only 2 patients (6.7%), which the authors attribute to earlier detection or improved surgical excision rather than any drug effect. The same series notes that 23 of 31 patients had in situ or pagetoid disease, and that local surgical excision was the initial treatment in 25 patients, with exenteration in 4.
Immunohistochemical work from 2006 on 27 sebaceous lesions, including 8 carcinomas, found that carcinomas had significantly increased p53 (50% versus 11%) and Ki-67 (30% versus 10%) expression compared with adenomas, and significantly reduced bcl-2 (7% versus 56%) and p21 (16% versus 34%). Critically, the authors report little or no Her-2/neu and CD117 staining, concluding that immunotherapy with Herceptin or Gleevec would likely not be useful for sebaceous carcinomas. A 2013 case of a rapidly growing eyelid sebaceous adenoma used fluorescence in situ hybridisation and found low human epidermal growth factor receptor 2 amplification, supporting the view that HER2-directed agents have no clear role in these tumours.
Case reports dominate the recent literature. A 2019 report of a giant extraocular chest wall sebaceous carcinoma in a 45-year-old HIV-positive man describes wide excision as the standard treatment, with no mention of adjuvant systemic therapy. A 2020 case of a rapidly growing upper back mass was managed with wide surgical excision alone, and the authors explicitly note that sparse literature exists to guide management and that further studies are needed to investigate therapeutic interventions. A 2020 case report of a 74-year-old man with eyelid sebaceous carcinoma misdiagnosed initially describes orbital exenteration, partial parotidectomy and cervical lymphadenectomy after tumour invasion of the medial rectus muscle and spread to the parotid gland; adjuvant radiotherapy was offered but complicated by radio necrosis requiring surgical reconstruction. No drug treatment is described in any of these cases.
The recurring theme across all abstracts is diagnostic delay and misdiagnosis, with the 2016 review stating that morbidity and metastasis rates remain high despite advances in immunohistochemistry and treatment options, and that prognosis is strongly related to time between diagnosis and treatment initiation. What is missing is any prospective trial of systemic therapy for sebaceous carcinoma, any data on chemotherapy or checkpoint inhibitors, and any molecular characterisation that would support a specific targeted agent. Patient stratification by stage or biomarker status does not exist in this literature, and funding for a rare cancer with no established drug pathway would be required before any repurposing hypothesis could be tested.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ophthalmic Plastic and Reconstructive Surgery · 2008 · 143 citations
Sebaceous Cell Carcinoma of the Ocular Adnexa: Clinical Presentations, Histopathology, and Outcomes
AbstractPURPOSE: To investigate the clinical features, time to diagnosis, histopathology, treatment, and mortality rates of patients with sebaceous cell carcinoma. METHODS: This was a retrospective, consecutive series of patients with sebaceous cell carcinoma at a tertiary referral medical center. Between January 1984 and January 2006, 31 patients with sebaceous cell carcinoma were evaluated at the Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics. The main outcome measures were clinical presentations, treatments, reconstructive procedures, and outcomes. RESULTS: Thirty-one patients were diagnosed with sebaceous cell carcinoma of the ocular adnexa on histopathology. Twenty (65%) of the patients were women and 11 were men. The upper eyelid was involved in 18 patients, lower eyelid in 10, both upper and lower eyelids in 1, and caruncle in 2. Twenty-three patients had in situ disease, pagetoid disease, or both. Eight patients reported symptoms for <6 months and 22 had symptoms for < or = 12 months before the diagnosis of sebaceous cell carcinoma was made. Local surgical excision of the tumor as initial treatment was performed in 25 patients. Exenteration was the initial surgery performed in 4 patients. Two patients died from metastatic sebaceous cell carcinoma. CONCLUSIONS: Sebaceous cell carcinoma has varied presentations and is commonly misdiagnosed. Tumor-related deaths occurred in only 2 patients (6.7%), which is lower than previous reports and may be related to earlier detection or improved surgical excision techniques.
American Journal of Dermatopathology · 2006 · 88 citations
Distinction of Benign Sebaceous Proliferations From Sebaceous Carcinomas by Immunohistochemistry
AbstractSebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.
Clinical Cancer Research · 2020 · 46 citations · open access
Sebaceous Carcinoma Epidemiology and Genetics: Emerging Concepts and Clinical Implications for Screening, Prevention, and Treatment
AbstractSebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Finally, we review the clinical implications of recent advances in sebaceous carcinoma research for screening, prevention, and treatment.
Clinical ophthalmology · 2013 · 14 citations · open access
A case of sebaceous adenoma of the eyelid showing excessively rapid growth
AbstractBACKGROUND: Sebaceous adenomas are found mainly in elderly individuals and are usually tan, pink, or yellow nodules or papules, usually approximately 5 mm in the largest size. CASE REPORT: A 65-year-old man presented with a progressively enlarging exophytic lesion in the right eyelid for 3 months. External examination revealed a yellowish-pink growth measuring 18 × 13 × 14 mm. The lesion surface was covered by palpebral conjunctiva with fine papillary projections, vascularity, crusting, and ulceration. Two weeks later, the growth enlarged to 20 × 14 × 14 mm, and ulceration also expanded. An excisional biopsy with clear resection margins was performed. No malignancy was found in the stump. Histopathologically, the lesion was located principally within the cutaneous compartment and composed of multiple circumscribed sebaceous lobules, separated, and exhibiting no cytologic atypia. Cystic change was not evident, and no infiltrative growth pattern, pagetoid lesions, mitotic figures, and lymphovascular space invasion were observed. The Ki-67 nuclear antigen was detected in 10%-15% of cells located in the basal zone of the nodule. Fluorescence in situ hybridization showed low human epidermal growth factor receptor 2 amplification, suggesting no genetic changes. The clinical findings, lack of infiltrative border, low Ki-67 index, and low proliferative ability support a diagnosis of sebaceous adenoma. CONCLUSION: Sebaceous adenoma that shows excessively rapid growth due to hyperplasia may appear to be malignant. Histopathology, fluorescence in situ hybridization, and Ki-67 were useful to the diagnosis of the adenoma. Excisional biopsy with clear resection margins must be performed in rapidly growing tumors.
International Journal of Surgery Case Reports · 2019 · 8 citations · open access
A rare giant extraocular, anterior chest wall sebaceous carcinoma
AbstractBACKGROUND: Sebaceous carcinoma (SC) is a rare aggressive cutaneous malignant tumour. It accounts for less than 1 % of all cutaneous malignant tumours. Sebaceous carcinomas are divided into ocular and extraocular constituting 75 % and 25 % respectively. The most common extraocular site is parotid gland. Chest wall is a rare site of this tumour. CASE PRESENTATION: In line with SCARE criteria (Agha et al., 2018 [1]), this report is a case of a 45-year-old African male patient who presented with a two-year history of a large right anterior chest wall tumour. He reported that the tumour started as a small lump, which grew gradually over a two-year period. The patient reported no history of visceral malignancy and radiation exposure. However, his risk factors were age and immunosuppression in the form of Human Immunodeficiency Virus (HIV). The tumour was initially diagnosed as sebaceous adenocarcinoma by incisional biopsy before the patient had been referred to the treating team a year before. Excision of the tumour with wide margins was undertaken, and histology results confirmed sebaceous carcinoma. DISCUSSION: Sebaceous carcinoma is a rare and aggressive adnexal tumour. It is categorized as ocular and extraocular. Of these two, the more common is extraocular. The chest wall is a rare site for this tumour. The definitive diagnosis of this kind of tumour is done by tissue biopsy. In dealing with this tumour, surgical excision with wide margins is the standard treatment. CONCLUSION: Sebaceous carcinoma is a rare aggressive malignant tumour originating from sebaceous gland. Early diagnosis and wide excision with negative margins improves survival.
Journal of Clinical & Experimental Dermatology Research · 2016 · 6 citations
Sebaceous Cell Carcinoma: A Persistent Challenge in Clinical and Histopathological Diagnosis
AbstractSebaceous cell carcinoma continues to defy clinicians and pathologists in terms of early diagnosis. The tumor may be mistaken as benign lesions such as chalazion and blepharitis, and also as malignant neoplasms, mainly basal cell carcinoma and squamous cell carcinoma. Despite advances in immunohistochemical analysis and treatment options during the last decades, morbidity and metastasis rates remain high. Prognosis is strongly related to the length of time between diagnosis and initiation of treatment, which reinforces the importance of early recognition of this condition. This article reviews key features of sebaceous cell carcinoma, from epidemiology to treatment, and new strategies to improve outcome.
Extraocular sebaceous carcinoma as a rapidly growing back mass: a case report
AbstractSebaceous carcinoma is a rare cutaneous malignancy that frequently mimics other dermatologic conditions. Extraocular subtypes are uncommon, but when present are frequently located in the head and neck region. Herein, we present a patient with a rapidly growing upper back mass eventually diagnosed as sebaceous carcinoma and managed with wide surgical excision. Currently, sparse literature exists to guide management of such patients. This case highlights not only the diagnostic challenges of sebaceous carcinoma, but also the need for further studies to investigate therapeutic interventions and long-term outcomes.
AbstractBACKGROUND: Sebaceous carcinoma is an aggressive malignant tumour. To prevent mutilating surgery and improve patient outcomes, early diagnosis and prompt treatment are necessary. When the tumour invades surrounding tissues, treatment may become complex. METHODS: We present a case report illustrating complex resection and reconstruction of a sebaceous carcinoma after initial misdiagnosis. RESULTS: A 74-year-old man with a sebaceous carcinoma to his right upper eyelid had a delay in treatment due to initial misdiagnosis. Upon the correct diagnosis, computed tomography scan showed tumour invasion of the medial rectus muscle and tumour spread to the right parotid gland. An orbital exenteration, partial parotidectomy and selective cervical lymphadenectomy were performed. Frozen section examination showed false-free margins, as additional paraffin embedded sections showed uncomplete tumour resection. Adjuvant radiotherapy was offered to the patient. The treatment was complicated by radio necrosis, necessitating surgical reconstruction by a paramedian forehead flap. Final reconstruction of the right orbit was accomplished by a personalised epithesis. CONCLUSIONS: Sebaceous carcinoma is a tumour that is often misdiagnosed. The aim of this case report is to emphasize the possible consequences of its misdiagnosis. An overview of characteristic clinical findings is provided to help reduce the number of misdiagnoses.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
