DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Vulvar Squamous Cell Carcinoma — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVulvar Squamous Cell Carcinoma maps to a 44-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 vulvar 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
Vulvar squamous cell carcinoma is an uncommon gynaecological malignancy primarily affecting postmenopausal women. There is no specific screening; the most effective strategy to reduce incidence is treatment of predisposing and preneoplastic lesions. Most women present with vulvar pruritus, pain, or a lump or ulcer. Standard therapy for early-stage disease is surgical: wide radical excision of the primary tumour with inguinal-femoral lymphadenectomy or sentinel lymph node mapping. For locally advanced or metastatic disease, neoadjuvant or definitive chemoradiation is often considered as an alternative. In a retrospective cohort of 50 patients with squamous cell carcinoma of the vulva, 52% presented with Stage III disease; 36 of 50 underwent surgery, and 40 received radiotherapy. At a median follow-up of 25.5 months, median overall survival was 31 months and median disease-free survival was 25 months; 42% of patients were alive and free of disease at last follow-up.
Evidence for systemic treatment in advanced, recurrent, or metastatic vulvar cancer is poor. Few clinical trials have been performed, and indication criteria vary widely among countries and institutions. In a retrospective case series from a single centre, 12 of 291 patients (4.1%) with vulvar squamous cell cancer received at least one targeted therapy after a median of 3.5 previous lines of platinum-based chemotherapy. In the erlotinib subgroup, two of five patients (40%) achieved stable disease and two of five (40%) experienced partial response; treatment was given as monotherapy in second or third line for a median of 3.4 months. Bevacizumab was given as maintenance after platinum-based first-line chemotherapy in nine patients; best response was complete response in two of nine (22.2%), with a median treatment duration of 7 months. In the pembrolizumab subset of three patients, best response was stable disease in one (33%); treatment was given as monotherapy in second or third line for a median of 3.3 months. Nine of 12 patients (75%) experienced treatment-related adverse events, most commonly grade 1 or 2.
Concurrent chemoradiation is considered an effective alternative for advanced tumours, but there is no standard therapy for advanced disease. In the retrospective cohort, patients who received intensity-modulated radiotherapy had significantly less grade 2 or more skin toxicity compared with conventional radiotherapy, and fewer required treatment breaks. The authors note that intergroup trials are needed to clarify the value of chemoradiation, neoadjuvant chemotherapy, and targeted therapy in advanced squamous cell cancer of the vulva. Rapidly evolving antibody treatments have proven clinical benefit in HPV-driven tumour entities, but clinical investigations in vulvar squamous cell carcinoma are still limited.
What is still missing: adequately powered multicentre trials that can identify the most effective systemic and targeted regimens; prospective data on patient stratification by HPV status, PD-L1 expression, or EGFR mutation; and dedicated funding for a rare disease where the level of evidence for different treatment modalities remains poor.
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 Gynecology & Obstetrics · 2021 · 171 citations · open access
Cancer of the vulva: 2021 update
AbstractVulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.
International Journal of Gynecology & Obstetrics · 2018 · 152 citations · open access
Cancer of the vulva
AbstractVulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized, and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.
Expert Review of Anticancer Therapy · 2015 · 42 citations
Systemic treatment of vulvar cancer
AbstractSquamous cell carcinoma of the vulva is a rare disease, accounting for approximately 5% of cancers of the female genital tract. Standard therapy for early-stage vulvar cancer mainly comprises of surgery of the vulva and groins. In locally advanced or metastatic vulvar cancer, neoadjuvant or definitive chemoradiation is often considered as an alternative treatment option. Given its rarity, the level of evidence for different treatment modalities is poor and few clinical trials have been performed on this disease. Therefore indication criteria for systemic treatment in advanced stage vulvar cancer vary widely among countries and institutions. This review focuses on the different systemic treatment options for patients with locally advanced, recurrent or metastatic vulvar cancer, and highlights the need for an international multicenter approach to identify the most effective therapeutic options.
Journal of obstetrics and gynaecology research · 2014 · 38 citations
Management of squamous cell vulvar cancer: A review
AbstractSquamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment for early stage disease consists of wide radical excision of the primary tumor with inguinal-femoral lymphadenectomy or sentinel lymph node mapping/biopsy. Because of the general paucity of patients with advanced vulvar cancer, there is no standard therapy for advanced disease and therefore treatment should be individualized. Intergroup trials are needed to clarify the value of chemoradiation, neoadjuvant chemotherapy and targeted therapy in patients with advanced squamous cell cancer of the vulva to identify modalities with the best therapeutic index and lowest morbidity.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · 2020 · 28 citations · open access
Targeted Therapeutic Approaches in Vulvar Squamous Cell Cancer (VSCC): Case Series and Review of the Literature
AbstractTherapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 20132019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: vulvar cancer AND targeted therapy, erlotinib, EGFR, bevacizumab, VEGF, pembrolizumab, or immunotherapy. Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients [median 3.5 previous lines (range 25)]. In the erlotinib subgroup, two of five patients (40%) achieved stable disease (SD), while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in second/third line for a median of 3.4 months (range 26 months). Bevacizumab (n=9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9); best response was complete response (CR) (n=2/9 22.2%). Median duration of treatment was 7 months (range 413 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n=3) subset was SD (n=1/3 33%). Treatment was given as monotherapy in second/third line for a median of 3.3 months (range 34 months). Nine of 12 patients (75%) experienced treatment-related adverse events (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities; however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.
South Asian Journal of Cancer · 2019 · 7 citations · open access
Conventional radiotherapy and intensity-modulated radiotherapy in carcinoma vulva: An experience from a tertiary medical center of India
AbstractAbstract Context: Vulvar cancer is one of the uncommon gynecological malignancies. Multimodality treatment with surgery, radiotherapy, and chemotherapy are required for treatment of the disease. Aims: The aim of the study was to evaluate clinical outcome in patients of carcinoma vulva, treated at our institution. Subjects and Methods: This was a retrospective-cohort study done in 50 patients with squamous cell carcinoma of the vulva, treated at our institution from January 2008 to December 2014. Data were analyzed on the basis of age, stage, type of treatment received, and treatment-related toxicity. Disease-free survival and overall survival were estimated. Statistical Analysis Used: Kaplan–Meier survival analysis and Chi-square test were used for statistical analysis. Results: Majority of the patients (52%) had presented with Stage III disease. Thirty-six of 50 patients underwent surgery: simple vulvectomy – 2, radical vulvectomy – 34, bilateral inguinal lymph node dissection was done in 32 patients, and 1 patient underwent ipsilateral-inguinal lymph node dissection. Among 40 patients who received radiotherapy and eight patients received palliative radiotherapy. Seventeen patients underwent intensity-modulated radiotherapy (IMRT) and 15 patients received conventional radiotherapy. Significantly less Grade 2 or more skin toxicity (P = 0.003) observed in patients who underwent IMRT. Among non-IMRT group, eight patients required treatment break during radiation. At a median follow-up time of 25.5 months, median overall survival was 31 months and median disease-free survival was 25 months. About 42% patients were alive and free of disease at last follow-up. Conclusions: Modified radical vulvectomy with inguinal lymph node dissection followed by radiotherapy is the mainstay of management of locally advanced carcinoma vulva. Using IMRT, we could minimize the treatment related radiation toxicity and treatment breaks.
Case Reports in Oncological Medicine · 2019 · 3 citations · open access
A Case of Stage I Vulvar Squamous Cell Carcinoma with Early Relapse and Rapid Disease Progression
AbstractSquamous cell carcinoma (SCC) is the most common subtype of vulvar cancer. Locoregional surgery is often curative when the tumor is diagnosed at an early stage. However, the disease can unexpectedly evolve with a dismal prognosis even after an early diagnosis. We report a case of a woman who experienced a rapid, chemorefractory tumor progression after surgery for stage IB vulvar SCC.
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.
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