DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Anal Squamous Cell Carcinoma — 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 moduleAnal Squamous Cell Carcinoma 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
No approved-drug candidate for anal squamous cell carcinoma 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
mitogen-activated protein kinase 1 (MAPK1) — MAPK1 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 2~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AOJ · 1.12 Å · ligand 1-[(2~{S})-2-(5-methyl-3-pyridin-4-yl-1~{H}-pyrazol-4-yl)pyrrolidin-1-yl]propan-1-one (N8L). Experimental structure, not a prediction.
What the evidence adds up to
Anal squamous cell carcinoma is a rare malignancy, accounting for roughly 2% of gastrointestinal tract cancers, with an incidence that has been rising steadily for at least a decade. Human papillomavirus infection and immunosuppression are the major risk factors. Chemoradiation remains the mainstay of treatment for early-stage disease, while systemic therapy is used for metastatic disease. Salvage surgery is reserved for persistent or recurrent disease after chemoradiation. One review notes that access to novel cytotoxic combinations and immunotherapy has improved outcomes for advanced disease, but does not give specific survival or response numbers. Another review from 2014 states that the incidence of anal cancer has risen about 2% each year over the prior decade.
The role of chronic inflammation in anal cancer development is accepted, based on mechanisms that promote cellular transformation and allow tumour cells to avoid apoptosis and immune surveillance. However, the molecular and cellular mechanisms remain largely unexplored. A 2016 study of 43 Brazilian anal tumours (23 squamous cell carcinomas, 11 adenocarcinomas, and 9 high-grade squamous intraepithelial lesions) found that KRAS and BRAF mutations are rare. Only one squamous cell carcinoma (2.3%) had a KRAS p.G13D mutation, and one adenocarcinoma (2.3%) had a BRAF p.V600E mutation. The authors conclude that most patients would not benefit from targeted therapies based on these mutations, and that other molecular alterations likely drive anal cancer development.
Anal high-grade squamous intraepithelial lesion (HSIL) is a precancerous condition for anal squamous cell carcinoma. A 2024 review of treatment modalities for anal HSIL covers topical medications, ablation, and surgery, but provides no quantitative results on efficacy, recurrence rates, or long-term outcomes. The review aims to optimise future treatment but does not report data from any specific trial.
What is still missing are large, prospective clinical trials with clearly defined endpoints for both HSIL and invasive anal cancer. The molecular drivers beyond HPV and rare KRAS/BRAF mutations remain unidentified, which limits patient stratification for targeted therapy. Funding for translational research linking inflammation pathways to immunotherapy response is lacking, as are robust biomarkers to predict which patients will benefit from chemoradiation versus salvage surgery or systemic therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Oncology · 2023 · 80 citations · open access
Anal Cancer: The Past, Present and Future
AbstractAnal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. The management of anal cancer has evolved over the past several decades and continues to do so. Chemoradiation therapy remains the mainstay for treatment for most patients with early-stage disease, whereas systemic therapy is the primary treatment for patients with metastatic disease. Patients with persistent disease or recurrence following chemoradiation therapy are treated with salvage surgery. Access to novel cytotoxic combinations and immunotherapy has improved the outcomes of patients with advanced disease. This review provides an overview of advances in the management of anal cancer over the past two decades. This paper reviews the epidemiology, risk factors, pathology, diagnosis, and management of localized and advanced anal squamous cell cancer, highlights current knowledge gaps in the management of anal cancer, and discusses future directions.
World Journal of Gastroenterology · 2014 · 78 citations · open access
Anal squamous cell carcinoma: An evolution in disease and management
AbstractAnal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.
AbstractThe aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment.
Clinics in Colon and Rectal Surgery · 2018 · 6 citations · open access
So Now My Patient Has Squamous Cell Cancer: Diagnosis, Staging, and Treatment of Squamous Cell Carcinoma of the Anal Canal and Anal Margin
AbstractSquamous cell carcinomas of the anal canal and the anal margin are rare malignancies that are increasing in incidence. Patients with these tumors often experience delayed treatment due to delay in diagnosis or misdiagnosis of the condition. Distinguishing between anal canal and anal margin tumors has implications for staging and treatment. Chemoradiation therapy is the mainstay of treatment for anal canal squamous cell, with abdominoperineal resection reserved for salvage treatment in cases of persistent or recurrent disease. Early anal margin squamous cell carcinoma can be treated with wide local excision, but more advanced tumors require a combination of chemoradiation therapy and surgical excision.
Molecular Medicine Reports · 2016 · 2 citations · open access
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors
AbstractAnal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising ~95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV‑/p16‑and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high‑grade squamous intra‑epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto‑oncogene, GTPase (KRAS; codons 12 and 13) and B‑Raf proto‑oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation.
DOAJ (DOAJ: Directory of Open Access Journals) · 2024 · 0 citations
Research status of treatment modalities for anal high-grade squamous intraepithelial lesion
Abstract［Abstract］ Anal high-grade squamous intraepithelial lesion (HSIL), encompassing grades 2 and 3 of anal intraepithelial neoplasia, represents a precancerous condition for anal squamous cell carcinoma. Actively pursuing individualized interventions and effective follow-up management for these patients is significant. Based on relevant literature, this article reviews the current research status of topical medications, ablation, and surgical treatment for anal HSIL, aiming to provide insights for optimizing the treatment of this disease in the future.
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.
