DeCure for Colon small cell neuroendocrine carcinoma
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for colon small cell neuroendocrine carcinoma — screening already-approved drugs against its 27-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColon small cell neuroendocrine carcinoma maps to a 27-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 colon small cell neuroendocrine 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
KRas proto-oncogene, GTPase (KRAS) — KRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
From a single-institution series of 38 patients with colorectal neuroendocrine carcinomas (excluding carcinoid tumours) collected between 1975 and 1998, the median survival was 10.4 months. One-year survival was 46%, two-year survival 26%, and three-year survival 13%. Metastatic disease was present at diagnosis in 69.4% of patients (25 of 36 evaluable). The series included 22 small cell carcinomas and 16 large cell neuroendocrine carcinomas; survival did not differ significantly between these pathologic subtypes. Tumours were advanced at presentation: 6 patients had AJCC Stage I, 7 had Stage III, and 25 had Stage IV disease.
A multi-institutional study of 66 primary colorectal neuroendocrine carcinomas (36 small cell, 30 moderately differentiated) found that 23% of cases (15 of 66) showed strong, diffuse cytoplasmic staining for the c-kit protein (CD117) by immunohistochemistry. None of these kit-positive tumours had mutations in exon 11 of the c-kit gene, unlike gastrointestinal stromal tumours. Survival did not differ significantly between kit-positive and kit-negative patients (P = 0.77). The authors noted that specific tyrosine kinase inhibitors had shown promise in other kit-expressing malignancies, but the absence of activating mutations and the lack of survival difference suggested that c-kit overexpression is not an initiating event in these tumours.
A 1998 study reported that the ND4 monoclonal antibody, which recognises a tumour marker on poorly differentiated colorectal cancer, was expressed in 25% of gastrointestinal neuroendocrine tumours. Carcinoembryonic antigen (CEA) was expressed in 37% of cases. Serum detection of the ND4 marker was possible in some patients with neuroendocrine tumours, but reactivity was lower in patients with localised disease, and the authors judged the test unlikely to be of diagnostic utility in that group.
What remains missing is prospective data on any systemic therapy specifically for colon small cell neuroendocrine carcinoma. The available studies are retrospective, span decades, and report no treatment outcomes beyond survival. No trial has tested a targeted agent against c-kit in this subset, and no molecular stratification has been attempted in a prospective design. Funding for a dedicated trial, given the rarity of the disease, is the principal barrier.
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 · 2004 · 341 citations
Neuroendocrine Carcinomas of the Colon and Rectum
AbstractPURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29-86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6-263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for high-grade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.
The American Journal of Surgical Pathology · 2003 · 41 citations
Analysis of Protein Expression and Gene Mutation of c-kit in Colorectal Neuroendocrine Carcinomas
AbstractPrimary neuroendocrine carcinomas of the colon are rare but highly aggressive malignancies. The recent observations that c-kit protooncogene, a tyrosine kinase, is overexpressed in a subset of small cell lung cancer and that selective kinase inhibitors block the in vitro growth of small cell lung cancer cell lines prompted us to investigate the expression and mutation status of the c-kit gene in colorectal neuroendocrine carcinomas. Sixty-six cases of primary colorectal neuroendocrine carcinoma were collected from 13 institutions, including 36 small cell carcinomas and 30 moderately differentiated neuroendocrine carcinomas. Immunohistochemical studies using a polyclonal antibody against c-kit protein (CD117) demonstrated a strong and diffuse cytoplasmic staining in 15 cases (23%), which were relatively equally distributed in the small cell and moderately differentiated subgroups. As controls, 25 conventional colorectal adenocarcinomas, 26 colorectal adenomas and 19 colorectal carcinoid tumors were all negative, whereas 15 gastrointestinal stromal tumors were all positive, for kit expression. In contrast to gastrointestinal stromal tumors, kit-overexpressing neuroendocrine carcinomas showed no mutations in the juxtamembrane domain (exon 11) of the c-kit gene as determined by mutational analysis. Kaplan-Meier analysis with the log-rank test revealed that the patients with kit-positive tumors did not differ significantly in survival from those with kit-negative tumors (P = 0.77). These results indicate that c-kit overexpression observed in a subset of colorectal neuroendocrine carcinomas may not be mediated via activating mutations, and does not appear to be an initiating event during tumorigenesis because of lack of c-kit expression in other types of colorectal epithelial neoplasms. More importantly, our observations may have potential therapeutic implications since specific tyrosine kinase inhibitors have shown promise in the management of patients with kit-expressing malignancies.
World Journal of Gastroenterology · 2010 · 23 citations · open access
Pathologic research update of colorectal neuroendocrine tumors
AbstractColorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.
Journal of Medical Case Reports · 2013 · 6 citations · open access
Advanced small-cell colon carcinoma: a case report
AbstractINTRODUCTION: Small-cell colon carcinoma is a very rare disease among colon neoplasms; it is difficult to achieve long-term survival due to its aggressive tumor behavior. Here we report the long-term survival of a patient with advanced small-cell colon carcinoma achieved by a combination of surgery and continuous chemotherapy. CASE PRESENTATION: A 67-year-old Japanese man underwent abdominal computed tomography in our institution for follow up after gastrectomy, and abnormal thickness of the sigmoid colon wall was revealed. An endoscopy demonstrated a 20mm Bormann 2 lesion with central ulceration located 20cm from the anal verge. A sigmoidectomy was performed. Histologically, the tumor deeply invaded the tissue and extended beyond the serosa, and was diagnosed as small-cell carcinoma. Cisplatin plus irinotecan was administered for adjuvant chemotherapy. Nine months after surgery, a follow-up computed tomography showed an enlarged lymph node behind the inferior vena cava and a 15×8mm nodule located at the ventral side of the cecum. Under consideration of progressive disease, cisplatin plus irinotecan therapy was performed again using the same regimen. After nine cycles of cisplatin plus irinotecan therapy, a follow-up gastric endoscopy demonstrated external tumor invasion to the duodenum wall. Carboplatin plus etoposide therapy was selected as a third-line regimen. After six cycles of carboplatin plus etoposide therapy, the recurrence sites were maintained in a stable condition, and the survival time reached approximately 30 months after the initial surgery. CONCLUSIONS: We report the long-term survival of a patient with advanced small-cell colon carcinoma. In the future, the accumulation and analysis of rare cases that obtain a better survival time will contribute to clarifying neuroendocrine carcinoma biology, and help to improve the prognosis.
Cancer Detection and Prevention · 1998 · 5 citations
Shared Tumor Antigens in Colorectal Carcinoma and Neuroendocrine Tumors
AbstractND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated colorectal cancer. We demonstrate its expression in 25% of gastrointestinal neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly differentiated colorectal cancer cell line that does not express CEA or other tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors is detected in only five of seven patients with the carcinoid syndrome and two of four of those without evidence of the syndrome. However, the reactivity was less in the patients with localized disease, and this test is unlikely to be of diagnostic utility in this group of patients. The sharing of this antigen in colorectal cancer and neuroendocrine tumors is not universal, but does support the common-cell progenitor theory for the origin of these tumors.
Korean Journal of Gastroenterology · 2009 · 4 citations · open access
A Case of Large Cell Neuroendocrine Carcinoma of the Colon
AbstractNeuroendocrine carcinoma of the colon can be classified into small cell carcinoma and large cell neuroendocrine carcinoma. The incidence of neuroendocrine carcinoma is so low that the guidelines for the treatment of large cell neuroendocrine carcinoma of the colon are not established. The prognosis of large cell neuroendocrine carcinoma of the colon is worse than that of conventional adenocarcinoma of the colon. We report a case of large cell neuroendocrine carcinoma of the colon that treated with right hemicolectomy and 6th sequential combination chemotherapy of 5-fluorouracil and cisplatin. There has been no evidence of the recurrence of metastasis of tumor for 6 months.
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.
