DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pharyngeal squamous cell carcinoma — screening already-approved drugs against its 49-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePharyngeal squamous cell carcinoma maps to a 49-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 pharyngeal 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In a single-institution retrospective series of 138 partial and circumferential pharyngectomies for squamous cell carcinoma of the hypopharynx and larynx performed between 1992 and 2002, the 5-year overall survival after salvage pharyngectomy for radiation failure was 31% and after primary pharyngectomy was 38%. The 5-year disease-specific survival was 40% for salvage and 45% for primary surgery. Perioperative mortality was 3.6% and combined morbidity 70%; postoperative hypocalcemia occurred in 44% of patients, pharyngocutaneous fistula in 31%, and long-term stricture in 15%. On multivariable analysis, extracapsular spread was the only independent predictor of worse disease-specific survival.
A separate cohort of 55 patients with pharyngeal or pharyngolaryngeal squamous cell carcinoma (mostly T1–T2) treated with transoral laser surgery had a local control rate of 90% and overall survival of 78% at a median follow-up of 24 months. Feeding tubes were used in 37 patients and removed after a median of 7 days; median hospital stay was 13 days. Early complications included recurrent aspiration pneumonia in 7 patients, laryngeal obstruction requiring tracheotomy in 3, severe postoperative haemorrhage in 2, and self-limiting cervical emphysema in 4.
A retrospective comparison of 180 patients with squamous cell carcinoma of the posterior pharyngeal wall treated between 1997 and 2011 found a 5-year overall survival of 33.4% for the whole group. Patients who received surgery with or without radiotherapy had a 5-year survival of 43% versus 24.1% for those who received definitive radiotherapy or chemoradiotherapy. On multivariate analysis, current smoking, T3–T4 classification, well-differentiated histology, and non-surgical treatment were associated with reduced overall survival. The survival advantage of surgery was significant in T1–T2 disease but not in T3–T4 disease.
A population-based Danish study of 7300 patients with pharyngeal and laryngeal squamous cell carcinoma diagnosed between 2008 and 2017 reported that 3% had distant metastases at diagnosis and 8% developed distant metastases after treatment. The 1-year and 2-year overall survival for post-treatment metastases (27% and 13%) and for metastases at diagnosis (28% and 9%) were equally poor. The most common sites of distant spread were lung, bone, lymph nodes, and liver. Among oropharyngeal cancers, the location of metastases did not differ by p16 status, but 21% of post-treatment metastases in p16-positive patients occurred later than three years, compared with 7% in p16-negative patients. What remains missing are prospective trials that stratify patients by tumour site, p16 status, and resectability, and that compare modern radiotherapy techniques with surgery in a controlled design rather than retrospective comparisons subject to selection bias.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Head & Neck · 2006 · 82 citations
Primary and salvage (hypo)pharyngectomy: Analysis and outcome
AbstractBACKGROUND: Surgery for squamous cell carcinoma (SCC) arising or extending to the hypopharynx is generally reserved for advanced disease or salvage. The prognosis of patients requiring pharyngectomy is poor, and the perioperative morbidity is significant. The aim of the present study is to describe the disease-related and treatment-related outcomes of patients undergoing primary and salvage pharyngectomy for cancer of the hypopharynx and larynx over a 10-year period from a single institution. METHODS: We retrospectively reviewed 138 partial and circumferential pharyngectomies performed at a tertiary referral center between 1992 and 2002. There were 31 females and 107 males. The median age was 62 years (range, 27-81 years), and mean follow-up was 3.6 years. Salvage pharyngectomy for radiation failure was performed in 72 patients (52%), and in 66 patients (48%) pharyngectomy was performed as the primary treatment. RESULTS: The 5-year overall survival rate after salvage pharyngectomy was 31% and after primary pharyngectomy was 38%. The 5-year disease-specific survival (DSS) for salvage was 40% and after primary surgery was 45%. The 5-year local and regional control rates for salvage pharyngectomy were 71% and 70%, respectively, and for primary pharyngectomy were 79% and 67%, respectively. The perioperative mortality rate was 3.6%, and the combined morbidity rate was 70%. Postoperative hypocalcemia developed in 44% of patients, a pharyngocutaneous fistula developed in 31% of patients, and the long-term stricture rate was 15%. Variables adversely affecting DSS on univariate analysis were nodal metastases (p = .044), extracapsular spread (ECS) (p = .006), poorly differentiated tumors (p = .015), lymphovascular invasion (p = .042), and positive tumor margins (p = .026). ECS (p = .023) was the only independent prognostic variable on multivariable analysis; however, there was a trend toward significance for nodal metastases (p = .064) and tumor differentiation (p = .079). CONCLUSION: This study demonstrates that both salvage pharyngectomy and primary surgery for advanced disease are viable options with high locoregional control. However, this represents a high-risk group in terms of both operative morbidity and survival. Patients with nodal metastases, ECS, and poorly differentiated tumors are likely to succumb to their disease and should be selected for adjuvant therapy when possible.
Archives of Otolaryngology - Head and Neck Surgery · 2007 · 41 citations
Transoral Laser Surgery for Pharyngeal and Pharyngolaryngeal Carcinomas
AbstractOBJECTIVE: To assess early oncological and functional outcomes after transoral laser surgery in patients with pharyngeal or pharyngolaryngeal squamous cell carcinoma. DESIGN: Inception cohort, with a median follow-up of 24 months. SETTING: Tertiary university center. PATIENTS: Fifty-five consecutive patients with pharyngeal or pharyngolaryngeal squamous cell carcinoma (T1, 24 patients; T2, 28 patients; and T3, 3 patients) were included. Patients had to be eligible for open functional surgery, and exposure in suspension micropharyngoscopy had to be possible. INTERVENTIONS: The pharynx and larynx were exposed with a bivalved laryngopharyngoscope, and the resection of the tumor was performed with a carbon dioxide laser coupled to a microscope. Neck dissection was performed in 43 patients. It was not attempted in the other 12 patients for the following reasons: N0 neck and severe comorbidities (n = 6), microinvasive cancer (n = 3), patient's refusal (n = 1), inoperable N3 disease (n = 1), and rapid local recurrence (n = 1). Eighteen patients (33%) received adjuvant radiotherapy: 12 for neck disease and 6 for positive resection margins. MAIN OUTCOME MEASURES: Local control and overall survival at the median follow-up visit. Evaluation of complications, pain, and rehabilitation of swallowing capacity. RESULTS: At a median follow-up of 24 months, the local control rate was 90%, and the overall survival rate was 78%. There were 16 early postoperative complications: recurrent aspiration pneumonia (n = 7); laryngeal obstruction, which required tracheotomy (n = 3); severe postoperative hemorrhage (n = 2); and cervical emphysema, which resolved spontaneously (n = 4). Feeding tubes were necessary in 37 patients. They were removed after a median period of 7 days. The median pain score was 4 of 10 during the first postoperative week and 0 of 10 after 4 weeks. The median hospital stay was 13 days (15 days for patients with neck dissection). CONCLUSIONS: Transoral laser surgery for pharyngeal and pharyngolaryngeal squamous cell carcinoma is a safe and acceptable therapeutic modality in selected cases. Good local control and avoidance of tracheotomy can be expected in most cases. Oral food intake is immediate, but feeding tubes are required to avoid weight loss during the postoperative period. Frequent early problems include transient postoperative bronchoinhalations and pain.
AbstractMost of the cancers that arise in the mucosa of the upper aerodigestive tract, including the oral cavity, pharynx, and larynx, are squamous cell carcinomas. To date, although there are no primary mutations that have been discovered to cause these cancers, aberrant expression of a variety of
Acta Oncologica · 2021 · 10 citations · open access
Distant metastases in squamous cell carcinoma of the pharynx and larynx: a population-based DAHANCA study
AbstractBACKGROUND: In head and neck cancer, distant metastases may be present at diagnosis (M1) or occur after treatment (DM). It is unknown whether M1 and DM follow the same clinical development and share prognosis, as population-based studies regarding outcomes are scarce. Therefore, we investigated the incidence, location of metastases and overall survival of patients with M1 and DM. MATERIALS AND METHODS: Patients diagnosed with squamous cell carcinoma of the pharynx and larynx in Denmark 2008-2017 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database. We identified 7300 patients, of whom 197 (3%) had M1 and 498 (8%) developed DM during follow-up. RESULTS: The 5-year cumulative incidence of DM was 8%. 1- and 2-year overall survival for DM (27% and 13%) vs. M1 (28% and 9%) were equally poor. There was no significant difference in location of metastases for M1 and DM and the most frequently involved organs were lungs, bone, lymph nodes and liver, in descending order. In oropharyngeal squamous cell carcinomas, the location of metastases did not differ by p16-status. For p16-positive patients, 21% of DM occurred later than three years of follow-up compared to 7% of p16-negative patients. CONCLUSION: Incidence, location of metastases and prognosis of primary metastatic (M1) or post-treatment metastatic (DM) disease in pharyngeal and laryngeal squamous cell carcinoma are similar in this register-based study.
Medicine and Pharmacy Reports · 2022 · 4 citations · open access
Recurrent submandibular fistula after Sunitinib treatment in a patient with renal cell carcinoma: a case report
AbstractSunitinib is commonly used in the treatment of patients with renal cell carcinoma and is associated with serious side-effects. We present the first report of a recurrent submandibular fistula in a patient treated with sunitinib. A 68-year-old man was referred to our clinic for a cutaneous fistula situated on the right side of his lower jaw. The patient had been diagnosed with bone metastases from a renal carcinoma 2 years ago and had received a single 4 mg dose of zoledronic acid and subsequent treatment with sunitinib 37.5 mg once daily for the past 4 weeks. The patient was treated surgically by a perilesional incision and primary closure with sutures, advised on meticulous oral hygiene and was kept on an antimicrobial agent in the form of clindamycin. After reinitiating his oncological treatment with sunitinib the cutaneous fistula re-appeared and bone abnormalities were also detected on his X-ray. After 18 months a contralateral cutaneous fistula was observed along with a spontaneous avulsion of the patient's left molar. Repeat surgical treatment and sequestrectomy was performed with the subsequent histopathological examination revealing a suspicion of osteonecrosis of the jaw and an associated Actinomyces infection.
Expert Review of Anticancer Therapy · 2015 · 0 citations
Efficacy of crizotinib inhibiting specific molecular pathways in non-small-cell lung carcinoma
AbstractThe US FDA granted approval for crizotinib as the first-line treatment for patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearranged metastatic non-small-cell lung cancer, on November 20, 2013. Crizotinib is a customized and improved therapeutic option for patients with non-small-cell lung cancer that enhances overall survival without increasing toxicity. In the future, new targeted therapies may achieve additional indications for treating patients with lung cancer. This article summarizes data from crizotinib studies.
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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