DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Appendix Adenocarcinoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAppendix Adenocarcinoma maps to a 47-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 appendix 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
transforming growth factor beta receptor 2 (TGFBR2) — TGFBR2 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 6-methoxypyridin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5QIN · 1.57 Å · ligand N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide (J2V). Experimental structure, not a prediction.
What the evidence adds up to
In a 1981 series of 22 appendiceal adenocarcinoma cases, correct diagnosis was never made preoperatively and only in 38 per cent of cases intraoperatively. Overall five-year survival was 18.7 per cent, rising to 43.4 per cent in the curative resection group, with tumour grade the only significant factor determining resectability and prognosis. A 2023 retrospective cohort of 1,423 appendectomy specimens found neoplasia in 2.38 per cent (n=34); adenocarcinoma accounted for 26.4 per cent (n=9) of these. After a median follow-up of 44.4 months, mean survival in appendiceal adenocarcinoma patients was 55 per cent compared with 100 per cent in neuroendocrine tumour patients. Secondary complementary surgery was performed in 66.7 per cent of adenocarcinoma patients, with right hemicolectomy in three and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in three.
A 2021 analysis of 724 patients with appendiceal non-mucinous adenocarcinoma from the Surveillance, Epidemiology and End Results database found that 301 (41.6 per cent) received post-operative chemotherapy. Patients with metastatic disease were more likely to receive chemotherapy (OR=7.42, 95% CI: 5.34-10.39), as were those with poorly differentiated tumours (OR=2.10, 95% CI: 1.49-3.00). However, univariate and multivariable Cox regression found no significant overall or cancer-specific survival advantage for post-operative chemotherapy in the whole group. Only patients with widespread metastatic (Stage IV) but well differentiated tumours showed better 3-year survival (11.9 per cent overall, 11.5 per cent cancer-specific) and 5-year survival (7.8 per cent overall, 6.8 per cent cancer-specific) with post-operative chemotherapy. The authors concluded that only this subgroup should be considered for post-operative chemotherapy.
A 2013 case report describes a 68-year-old man with a 35-year history of ulcerative colitis who developed a T2 adenocarcinoma of the appendix extending to the cecectomy staple line. He refused proctocolectomy with J-pouch reconstruction and underwent right hemicolectomy instead; at four-year follow-up he was free of malignancy. A 2023 case report describes a 27-year-old man with Stage IV moderately differentiated adenocarcinoma invading the psoas muscle, treated with right hemicolectomy, adjuvant chemotherapy and hyperthermic intraperitoneal chemotherapy. A 2019 case report describes an elderly patient with a perforated appendicular adenocarcinoma treated with single-staged surgery and adjunct chemotherapy. A 1982 report of two cases notes that preoperative diagnosis is extremely difficult, and a 2008 report on locally advanced perforated appendiceal adenocarcinoma attached to terminal ileum, cecum and rectosigmoid illustrates management challenges ranging from simple appendectomy to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
What remains missing is prospective multidisciplinary trial evidence for post-operative chemotherapy in appendiceal adenocarcinoma, particularly outside the narrow Stage IV well differentiated subgroup. The rarity of the disease, frequent diagnostic delay, and lack of established surgical strategies for patients with concurrent ulcerative colitis mean that patient stratification by grade and stage, and long-term follow-up data, are still inadequate. No drug therapy is supported by the abstracts beyond the chemotherapy regimens mentioned in the context of case reports and the retrospective database analysis, and no efficacy claim can be made from these data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diseases of the Colon & Rectum · 1981 · 51 citations
Adenocarcinoma of the appendix
AbstractTwenty-two cases of appendiceal adenocarcinoma are reviewed. Correct diagnosis was not made preoperatively in any case, and in only 38 per cent of the cases was it made intraoperatively. Thirty-two per cent of the patients had second primary neoplasm, and in more than half of these cases, the neoplasms were most likely concurrent with the appendiceal tumors. The overall five-year survival rate of the 22 patients was 18.7 per cent, with a 43.4 per cent survival rate in the curative resection group. The grade of tumor differentiation was the only significant factor in determining curative resectability and prognosis.
Revista da Associação Médica Brasileira · 2023 · 8 citations · open access
Analysis of appendiceal neoplasms in 1,423 appendectomy specimens: a 10-year retrospective cohort study from a single institution
AbstractOBJECTIVE: This study aimed to reveal the incidence, clinicopathological, and oncological outcomes of appendiceal neoplasms. METHODS: This is a retrospective cohort study from a single institution. Patients with a pathological diagnosis of malignancy who underwent appendectomy between January 2011 and 2021 were included in the study, and groups were formed according to pathological type. Clinical, pathological, and oncological results were compared in these groups. RESULTS: The incidence of neoplasia was 2.38% (n=34) in a cohort of 1,423 appendectomy cases. Of the cases, 56% (n=19) were female. The median age in the entire cohort was 55.5 (range: 13-106) years. In the cohort, the rate of neuroendocrine tumor mucinous cystadenoma adenocarcinoma, and low-grade appendiceal mucinous neoplasm, according to the American Joint Committee on Cancer classification of appendiceal neoplasms, was 32.3% (n=11), 26.4% (n=9), 26.4% (n=9), and 14.7% (n=5), respectively. Neuroendocrine tumor patients (median age: 35 years) were younger than the other groups (p=0.021). Secondary complementary surgery was performed in 66.7% (n=6) of adenocarcinoma patients and 27.3% (n=3) of neuroendocrine tumor patients. Right hemicolectomy was performed in all neuroendocrine tumor patients requiring secondary surgery, while right hemicolectomy was performed in three adenocarcinoma patients and cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in three adenocarcinoma patients. After a median follow-up of 44.4 months (95% confidence interval: 18.6-70.1), the mean survival rate was 55% in appendiceal adenocarcinoma patients compared to 100% in neuroendocrine tumor patients. CONCLUSION: Appendiceal neoplasms are rare but remain an important cause of mortality. Appendiceal adenocarcinomas are associated with poorer oncological outcomes compared to other neoplasms.
Journal of Crohn s and Colitis · 2013 · 3 citations · open access
Appendiceal adenocarcinoma in a patient with chronic ulcerative colitis: What is the appropriate surgical procedure?
AbstractDear Sir, Restorative proctocolectomy with ileal pouch-anal anastomosis (RP/IPAA) is the surgical therapy of choice for patients with chronic ulcerative colitis (CUC).1 The association between appendiceal cancer and CUC with long-standing disease and pancolitis was reported.2–5 However, there were no established surgical intervention strategies for these patients. We report a case of CUC associated with an appendiceal adenocarcinoma undergoing a limited right sided hemicolectomy. A 68 year old male with a 35-year history of ulcerative colitis (UC) in remission on 5-aminosalicylic acid (5-ASA) developed right lower quadrant abdominal pain. An abdominal/pelvic CT scan noted a distended and inflamed appendix consistent with acute appendicitis, and the distal colon wall thickening. Recent colonoscopy showed no colonic dysplasia. He underwent laparoscopic appendectomy with caput cecectomy and preservation of ileocecal valve. Pathology revealed a T2 adenocarcinoma of the appendix that extended to the cecectomy staple line. The patient refused the preferred proctocolectomy with J-pouch reconstruction and underwent a right sided hemicolectomy. At 4-year follow up, he is free of malignancy, and in remission on oral 5-ASA with only one mild flare which was controlled after a course of corticosteroid enemas and 5-ASA. RP/IPAA has become the standard surgical intervention of chronic ulcerative colitis since 1978. However, the incidence of complications remains relatively high in contrast to the low mortality rate.1 In 1994, Odze et al.3 reported the first case of appendix adenocarcinoma in a patient with a 20-year history of CUC with pancolitis but no dysplasia. The patient underwent a total colectomy, appendectomy and ileostomy. Zannoni et al.4 in 1997 described a female patient with a 20-year history of CUC with slightly active pancolitis but no dysplasia and with a cystadenocarcinoma of the appendix who underwent a right hemicolectomy. Appendix adenocarcinoma associated with CUC of a 60-year-old with a 5-year history of left colon CUC without dysplasia who underwent an elective total proctocolectomy with ileostomy after the failure of medical treatment was published by Villanueva Saenz et al. in 2006.5 Appendix adenocarcinoma was then detected during the surgery. Unfortunately, there were no follow up data for any of these cases. This is the first report with a 4-year follow up after a right sided hemicolectomy for an appendiceal adenocarcinoma involved with CUC. Our patient would only accept a right sided hemicolectomy and has minimal disease activity with no malignancy recurrence after 4 years. Considering the high complication rate of RP/IPAA or ileostomy, the right sided hemicolectomy could be a conservative option for the patients with appendiceal adenocarcinoma with CUC and no colonic dysplasia. However, lifelong colonoscopic surveillance is required for any patient with less than total proctocolectomy. Ultimately, these patients must recognize that they may need completion proctectomy or restorative proctectomy. The authors declare that they have no conflict of interest.
International Journal of Surgery Case Reports · 2023 · 1 citations · open access
A case report of appendiceal adenocarcinoma extending from the retroperitoneum to the psoas muscle
AbstractINTRODUCTION: Invasive appendiceal adenocarcinoma is rare. We describe the first reported case of appendiceal adenocarcinoma invading the psoas muscle in a 27-year-old man. CASE PRESENTATION: The patient presented with lower right quadrant pain, persisting since the last two months. Computed tomography revealed a retroperitoneal mass with a central calcified focus in the right iliac fossa, with a mass effect on the adjacent iliopsoas muscle and apparent invasion of the cecal wall. CLINICAL DISCUSSION: Magnetic resonance imaging showed a retrocecal appendicular mass with central necrosis. Colonoscopy showed an extra luminal mass effect that caused bulging of the ileocecal valve. Biopsy revealed lymphoid hyperplasia of the mucosa of the terminal ileum, with no malignant changes. An elective right hemicolectomy was done along with ileotransverse anastomosis. Histopathology examination of the surgical specimen revealed a moderately differentiated adenocarcinoma (Stage IV). Hence, adjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy was employed. CONCLUSION: Non-specific symptoms and difficulties in reaching a diagnosis pre-operatively, may contribute to underreporting of appendiceal adenocarcinomas. Besides, few therapeutic options are available due to the rarity of this tumor. Complete surgical excision and/or chemotherapy may be lifesaving.
Journal of Surgical Case Reports · 2019 · 1 citations · open access
A diagnostic dilemma of appendicular mass in an elderly patient: a case report and literature review
AbstractPrimary appendicular adenocarcinoma is a rare tumor, mucinous variety, being most common. The case presentation highlights the unusual appearance and diagnostic dilemma of an appendicular adenocarcinoma. Our elderly patient presented with an ill-defined tender lump which later was diagnosed as a perforated appendicular adenocarcinoma, responsive to single-staged surgery and adjunct chemotherapy. We considered the single-staged surgery since the appendix was perforated and right colectomy would not aid the prognosis. High index of clinical suspicion for malignancy should be kept in mind for elderly patients presenting with an appendicular lump. Every effort should be made during the elective surgery to remove the mass during the single-staged surgery.
Primary adenocarcinoma of the appendix: A report of two cases
AbstractPrimary adenocarcinoma of the appendix is rare; approximately 200 cases have been reported. Preoperative diagnosis is extremely difficult. We report two cases with two distinctive histologic patterns of adenocarcinoma resulting in different outcomes. The classification and treatment of primary epithelial malignant tumors of the appendix are also discussed.
Annals of Palliative Medicine · 2021 · 0 citations · open access
Post-operative chemotherapy improves the survival of patients with well differentiated widespread metastatic appendiceal non-mucinous adenocarcinomas
AbstractBACKGROUND: Appendiceal adenocarcinoma is a very rare type of tumor, often asymptomatic in the early stages of development. Surgical resection is the most preferred intervention against appendiceal non-mucinous adenocarcinoma, but the efficacy of post-operative adjuvant chemotherapy is still unclear because the cancer is rare. Accordingly, we sought to characterize appendiceal non-mucinous adenocarcinoma profile that confers a better survival advantage for post-operative chemotherapy. METHODS: We analyzed patients with appendiceal non-mucinous adenocarcinoma in the Surveillance, Epidemiology and End Results database, histologically diagnosed for the cancer between 2004 and 2015. Nearly half of the patients first underwent surgery and thereafter received post-operative chemotherapy. Logistic regression, Kaplan-Meier, univariate and multivariate Cox analysis were performed to evaluate the odds ratio for the propensity of patients underweening chemotherapy, whereas hazard ratios were used to evaluate the overall as well as cancer-specific survival. RESULTS: Of the 724 patients with appendiceal non-mucinous adenocarcinoma who underwent surgery, 301 (41.6%) received post-operative chemotherapy. Notably, patients with metastatic appendiceal non-mucinous adenocarcinoma were more likely to receive chemotherapy (OR =7.42, 95% CI: 5.34-10.39, P<0.001), similar to those with poor pathologically differentiated cancer types (OR =2.10, 95% CI: 1.49-3.00, P<0.001). However, univariate and multivariable Cox regression analyses found no significant overall survival and cancer-specific survival advantage for patients put on postoperative post-operative chemotherapy. In the disease stage and pathological differentiation groups, only patients with widespread metastatic (Stage IV) but well differentiated tumors displayed better 3-year (11.9% in overall survival, 11.5% in cancer-specific survival) and 5-year survival rate (7.8% in overall survival, 6.8% in cancer-specific survival) to post-operative chemotherapy. CONCLUSIONS: Staging and grading of appendiceal non-mucinous adenocarcinoma is invaluable in guiding the rationale of post-operative chemotherapy. Findings of this research support the view that only patients with both of widespread metastatic but well differentiated appendiceal non-mucinous adenocarcinoma should be considered for post-operative chemotherapy. Nonetheless, further prospective multidisciplinary clinical trials are necessary to further discern the use chemotherapy after surgery in appendiceal non-mucinous adenocarcinoma patients.
On the cohomology of locally symmetric adele spaces as a module over the Hecke algebra
AbstractAppendiceal cancers may be difficult to diagnose even after comprehensive investigation. This report of locally advanced perforated appendiceal adenocarcinoma attached to the terminal ileum, cecum, and rectosigmoid illustrates the management challenges that require comprehensive knowledge of pathologic variations and range from simple appendectomy to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
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.
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