DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for sigmoid colon cancer — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSigmoid colon cancer maps to a 2-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 sigmoid colon cancer 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
mutS homolog 2 (MSH2) — MSH2 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8RB1 · 2.085 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Sigmoid colon cancers present at an earlier stage than other colon subsites. In a California Cancer Registry analysis of 82,926 cases, 30.5% of sigmoid cancers were Stage I at diagnosis, compared with 18.5% of proximal colon cancers. After adjustment for stage, grade, treatment, and lymph node examination, sigmoid cancers had a lower colorectal-cancer-specific mortality than proximal tumours (hazard ratio 0.88; 95% CI 0.85–0.92).
Surgical technique affects short-term recovery. In a case-controlled study of 26 patients who had hand-assisted laparoscopic anterior resection (HAL-AR) and 52 who had open surgery, the HAL-AR group had a lower incidence of immediate postoperative leukocytosis (38.5% vs 69.2%, p=0.009), needed fewer days of additional pain killers (1.2 vs 2.4 days, p=0.002), and passed first flatus earlier (postoperative day 3 vs day 4, p=0.021). There were no significant differences in hospital stay, complication rates, or mortality between the two groups. Centralisation of colorectal surgery to a single hospital in Sweden, comparing 64 patients treated before 1996 with 82 treated after, reduced reoperations (0 vs 6, p=0.005) and postoperative mortality (1 vs 5, p=0.047), and improved overall survival for curatively treated patients (relative risk 0.56; 95% CI 0.34–0.93).
Neoadjuvant chemotherapy for locally advanced sigmoid colon cancer is rarely used. In a National Cancer Database study of 23,597 patients with clinical T3/T4, N0-2, M0 disease, only 364 (1.5%) received neoadjuvant chemotherapy. Patients treated at academic centres (41%) and high-volume centres (27%) were more likely to receive it, and those with Medicare/Medicaid (39%) or private insurance (52%) were more likely than uninsured patients. After propensity-score matching, there was no difference in overall survival (p=0.20), R0 resection rate (p=0.090), or 30-day readmission rate (p=0.30) between the neoadjuvant chemotherapy group and the surgery-first group. The neoadjuvant group did show a higher rate of N2-to-N1 downstaging.
What is still missing is a prospective trial large enough to detect a survival benefit from neoadjuvant chemotherapy in sigmoid colon cancer, given that the existing retrospective data show no such benefit. The role of centralisation and minimally invasive surgery is supported only by observational studies with small numbers. Patient stratification by molecular subtype or by precise tumour location within the sigmoid is not addressed in these reports.
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 · 2009 · 130 citations
Tumor Subsite Location Within the Colon Is Prognostic for Survival After Colon Cancer Diagnosis
AbstractPURPOSE: Proximal colon cancers are more likely to present with advanced stage than distal cancers; however, previous reports conflict regarding the independent prognostic significance of tumor location on survival. We examined survival by colon cancer subsite location by use of data from the California Cancer Registry. METHODS: An analysis of colon cancer cases from 1994 to 2004 was conducted, with follow-up through 2006. Colon subsite location was defined as proximal colon (cecum, ascending colon, hepatic flexure), transverse colon, descending colon (splenic flexure, descending colon), and sigmoid colon. Subsite-specific survival analyses were conducted with use of the Kaplan-Meier method and Cox proportional hazards ratios. RESULTS: A total of 82,926 colon cancer cases were identified, including 40,078 proximal (48%), 8,023 transverse (10%), 8,657 descending (10%), and 26,168 sigmoid cancers (32%). A larger proportion of sigmoid cancers (30.5%) presented as Stage I compared with proximal (18.5%), transverse (16.8%), or descending colon cancers (20.1%). Proximal cancers had the greater proportion with high tumor grade (27%), and had a greater mean number of lymph nodes examined. There were no differences in treatment rendered when each colon subsite was stratified by stage. After adjustment for stage, grade, treatment, lymph node examination, and other relevant clinical variables, sigmoid cancers had decreased colorectal cancer-specific mortality compared with proximal tumors (hazards ratio = 0.88; 95% confidence interval, 0.85-0.92). CONCLUSIONS: In this analysis, sigmoid colon cancers were observed to have earlier stage, lower tumor grade, and independently decreased colorectal cancer-specific mortality compared with proximal tumors.
Annals of Coloproctology · 2013 · 7 citations · open access
Feasibility of Hand-Assisted Laparoscopic Surgery as Compared to Open Surgery for Sigmoid Colon Cancer: A Case-Controlled Study
AbstractPURPOSE: The aim of this study was to evaluate short-term clinical outcomes by comparing hand-assisted laparoscopic surgery (HALS) with open surgery for sigmoid colon cancer. METHODS: Twenty-six patients who underwent a hand-assisted laparoscopic anterior resection (HAL-AR group) and 52 patients who underwent a conventional open anterior resection during the same period were enrolled (open group) in this study with a case-controlled design. RESULTS: Pathologic parameters were similar between the two groups. The incidences of immediate postoperative leukocytosis were 38.5% in the HAL-AR group and 69.2% in the open group (P = 0.009). There were no significant differences between the two groups as to leukocyte count, hemoglobin, and hematocrits (P = 0.758, P = 0.383, and P = 0.285, respectively). Of the postoperative recovery indicators, first flatus, sips of water and soft diet started on postoperative days 3, 5, 7 in the HALS group and on days 4, 5, 6 in the open group showed statistical significance (P = 0.021, P = 0.259, and P = 0.174, respectively). Administration of additional pain killers was needed for 1.2 days in the HAL-AR group and 2.4 days in the open group (P = 0.002). No significant differences in the durations of hospital stay and the rates of postoperative complications were noted, and no postoperative mortality was encountered in either group. CONCLUSION: The patients with sigmoid colon cancer who underwent a HAL-AR had a lower incidence of postoperative leukocytosis, less administration of pain killers, and faster first flatus than those who underwent open surgery. Clinical outcomes for patients' recovery and pathology status were similar between the two groups. Therefore, a HAL-AR for sigmoid colon cancer is feasible and has the same benefit as minimally invasive surgery.
Effects of Centralization of Colorectal Surgery on the Outcome of Patients with Distal Sigmoid Colonic Cancer
AbstractBACKGROUND: In 1996, all colorectal surgery in the county of Vastmanland, Sweden, was centralized to the central District Hospital in Vasterås. A Colorectal Unit was established and modern surgical procedures were introduced. The aim of this study was to analyze the outcome for patients treated surgically for distal sigmoid colonic cancer before and after the centralization. METHODS: Hospital records of all patients with distal sigmoid colonic cancer, treated between 1991-1995, group 1 (n = 64), and 1996-2000, group 2 (n = 82), were studied retrospectively. RESULTS: In group 2, there were fewer reoperations (n = 0) than in group 1 (n = 6; p = 0.005) and the postoperative mortality was lower; one in group 2 compared with five in group 1 (p = 0.047). The amount of lymph nodes examined were higher and the length of distal surgical margin longer in group 2. Curatively treated patients in group 2 had better overall survival compared to group 1 (RR 0.56; 95% CI 0.34-0.93). CONCLUSION: Centralization of colorectal surgery resulted in an improvement of pathologic specimens and a decrease in postoperative reoperations and mortality in patients treated surgically for distal sigmoid colonic cancer. Moreover, the overall survival of curatively treated patients was improved.
Nationwide Outcomes After Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer—A Propensity Score-Matched Analysis
AbstractBackground The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. Methods The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. Results There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC ( P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival ( P = .20), R0 resection ( P = .090), or 30-day readmission rates ( P = .30) in the NAC cohort compared to the non-NAC cohort. Conclusions Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.
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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