DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for rectal neoplasm — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRectal neoplasm maps to a 42-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 rectal neoplasm 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
In a 2016 analysis of 47 rectal cancer patients, KRAS mutation status was found to be homogeneous within primary tumours, with mutations detected in 20 patients (43%), the majority affecting codon 35. Preoperative chemoradiotherapy did not alter the mutation pattern, and no intratumoral heterogeneity was proven in either pre-therapeutic biopsies or post-therapeutic resection specimens. The authors noted that assay sensitivity depended on the amount of viable tumour cells after chemoradiotherapy, with the SNaPshot method producing discordant results that were resolved by the therascreen KRAS test. This suggests that KRAS testing for anti-EGFR therapy decisions is feasible on both pre- and post-treatment samples, provided the analytical method is chosen with tumour regression in mind.
A population-based study from Burgundy, France, covering 827 patients diagnosed between 1976 and 1990, documented substantial improvements in rectal cancer outcomes over that period. Curative resection rates rose from 57.2% before 1981 to 77.0% after 1985, and operative mortality after curative surgery fell from 13.9% to 3.7%. Five-year crude survival increased from 25.8% to 42.6%, with age, stage and period of diagnosis as independent prognostic factors. A separate Chinese comparative study of 76 patients treated with conventional transanal excision and 53 with transanal endoscopic microsurgery found that the latter achieved a lower local recurrence rate during a median follow-up of 40 months, particularly for tumours larger than 3 cm, located higher than 8 cm from the anal verge, and for pT1 carcinomas, though operation time was longer.
A 2023 retrospective review of 368 rectal cancer patients treated between 2008 and 2018 reported that the most dangerous site for pelvic recurrence remains the anastomotic site, and concluded that the debate over laparoscopic, robotic or open surgical approaches remains open. A 2015 review stated that chemoradiotherapy is the method of choice as the first stage of treatment for local recurrences, but its application is limited by prior pelvic radiotherapy, and surgery is the only potentially curative option, reserved for patients with a high probability of R0 resection. A 2013 review argued that radiotherapy alone or local excision combined with radiotherapy can achieve satisfactory results compared with radical surgery for early rectal carcinoma, while avoiding high rates of complications and adverse reactions.
A 2007 cDNA microarray study of 21 rectal cancer patients identified 23 up-regulated and 15 down-regulated genes in at least five samples, and hierarchical clustering separated patients into groups above and below stage II, suggesting expression profiles could aid tumour classification. A 1936 commentary described the abdominoperineal resection as the ideal operation, emphasising wide excision of the rectum, bowel above and below the lesion, and mesentery and pelvic contents. What remains missing across this literature is prospective, randomised evidence comparing modern minimally invasive techniques against each other and against open surgery for recurrent disease, along with validated biomarkers to stratify patients for organ-preserving approaches versus radical resection, and long-term functional outcome data beyond survival figures.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2016 · 19 citations · open access
Heterogeneity of KRAS Mutation Status in Rectal Cancer
AbstractINTRODUCTION: Anti-EGFR targeted therapy is of increasing importance in advanced colorectal cancer and prior KRAS mutation testing is mandatory for therapy. However, at which occasions this should be performed is still under debate. We aimed to assess in patients with locally advanced rectal cancer whether there is intra-specimen KRAS heterogeneity prior to and upon preoperative chemoradiotherapy (CRT), and if there are any changes in KRAS mutation status due to this intervention. MATERIALS AND METHODS: KRAS mutation status analyses were performed in 199 tumor samples from 47 patients with rectal cancer. To evaluate the heterogeneity between different tumor areas within the same tumor prior to preoperative CRT, 114 biopsies from 34 patients (mean 3 biopsies per patient) were analyzed (pre-therapeutic intratumoral heterogeneity). For the assessment of heterogeneity after CRT residual tumor tissue (85 samples) from 12 patients (mean 4.2 tissue samples per patient) were analyzed (post-therapeutic intratumoral heterogeneity) and assessment of heterogeneity before and after CRT was evaluated in corresponding patient samples (interventional heterogeneity). Primer extension method (SNaPshot™) was used for initial KRAS mutation status testing for Codon 12, 13, 61, and 146. Discordant results by this method were reevaluated by using the FDA-approved KRAS Pyro Kit 24, V1 and the RAS Extension Pyro Kit 24, V1 Kit (therascreen® KRAS test). RESULTS: For 20 (43%) out of the 47 patients, a KRAS mutation was detected. With 12 out of 20, the majority of these mutations affected codon 35. We did not obtained evidence that CRT results in changes of the KRAS mutation pattern. In addition, no intratumoral heterogeneity in the KRAS mutational status could be proven. This was true for both the biopsies prior to CRT and the resection specimens thereafter. The discrepancy observed in some samples when using the SNaPshot™ assay was due to insufficient sensitivity of this technique upon massive tumor regression by CRT as application of the therascreen® KRAS test revealed concordant results. CONCLUSION: Our results indicate that the KRAS mutation status at the primary tumor site of rectal cancer is homogenous. Its assessment for therapeutic decisions is feasible in pre-therapeutic biopsies as well as in post-therapeutic resected specimens. The amount of viable tumor cells seems to be an important determinant for assay sensitivity and should thus be considered for selection of the analytical method.
Population‐based study of the treatment and prognosis of carcinoma of the rectum
AbstractBACKGROUND: Few population-based studies address the issue of treatment of carcinoma of the rectum (15 cm or less from the anal verge) both from surgical and epidemiological aspects. METHODS: Some 827 patients were analysed in the cancer registry of the Côte-d'Or (Burgundy, France) from 1976 to 1990 (493,931 inhabitants). RESULTS: Resection for cure increased from 57.2 per cent before 1981 to 77.0 per cent after 1985 (P < 0.001), and the proportion of Dukes A and B cases from 35.8 to 52.5 per cent (P < 0.001). Among patients resected for cure, continence-preserving resections were performed more frequently during the 1986-1990 period (48.0 per cent) than during the two previous 5-year periods (20.0 per cent; P < 0.001), more often in women, in the upper half of the ampulla and for tumours of less than 45 mm. The operative mortality rate after curative surgery decreased from 13.9 to 3.7 per cent (P < 0.001) between the first and the last period whereas the 5-year crude survival rate rose from 25.8 to 42.6 per cent (P < 0.001). Age, stage of disease and period of diagnosis were independent prognostic factors of death in a relative survival model. CONCLUSION: This study indicates that significant advances have been achieved at a population level in the treatment of rectal cancer in terms of diagnosis, continence-preserving procedures and survival.
Local Resection for Rectal Tumors: Comparative Study of Transanal Endoscopic Microsurgery versus Conventional Transanal Excision – The Experience in China
AbstractBACKGROUND/AIMS: To compare the operative range,safety and therapeutic effect of local resection of rectal tumors by using transanal endoscopic microsurgery and conventional transanal excision. METHODOLOGY: We reviewed data from 76 patients treated using conventional TAE during the period from January 2003 to July 2006 and 53 patients treated using TEM during the period from September 2006 to February 2010 in the Ruijin Hospital affiliated with the Shanghai Jiaotong University School of Medicine. RESULTS: Age, gender, tumor size, blood loss and postoperative hospital stay were similar in the 2 groups. The median distance from the anal verge was significantly higher in the TEM group than in the TAE group. Operation time was significantly longer in the TEM group than in the TAE group.During the median follow-up of 40 months, the LRR in the TEM group was lower than that in the TAE group,especially for tumors that are larger (>3cm) and located higher (>8cm from the anal verge) and pT1 carcinomas. CONCLUSIONS: TEM is a safe, effective and minimally invasive surgical technique for the treatment of early rectal neoplasms. Compared to conventional TAE,TEM has a broader operative range and a better therapeutic effect.
IMPROVEMENTS IN THE TREATMENT OF CANCER OF THE RECTUM
AbstractWithin the past few years there has been definite and important progress in the management of cancer of the rectum. The fundamental principles underlying the successful treatment of this condition have long been established as regards both palliative procedures for temporary benefit and the curative or radical operations that give some encouraging prospect of relief. An understanding of the extension of cancer of the rectum beyond the primary site soon led to better results. The earlier observations, of W. Ernest Miles, 1 but recently reviewed by him, led to the general acceptance of the abdominoperineal resection as the ideal operation. The operation for cancer of the rectum must attempt to remove the involved rectum, an appreciable portion of bowel above and below the lesion and as wide an excision of mesentery and pelvic contents as possible. With this in mind, I strongly believe that the most radical operation should be
DOAJ (DOAJ: Directory of Open Access Journals) · 2015 · 1 citations · open access
RECTAL CANCER RECURRENCES FOLLOWING SURGICAL AND COMBINED TREATMENT: RISK FACTORS, DIAGNOSTICS AND TREATMENT
AbstractDiagnostic and treatment of rectal cancer local recurrences, risk factors and treatment tactics are discussed in this article. Chemoradio-therapy is a method of choice as the first stage of treatment for this patient group, however its application is limited by pelvic radiotherapy anamnesis. Surgery is the only method of potentially curative treatment, but it should be applied only in patients with high probability of R0-resection.
World Journal of Gastroenterology · 2007 · 1 citations
Identification of the differential expressive tumor associated genes in rectal cancers by cDNA microarray
AbstractAIM: To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors. METHODS: Rectal cancer tissues and their paired normal mucosa were obtained from patients undergoing surgical resection of rectal cancer. Total RNA was extracted using Trizol reagents. First strand cDNA synthesis was indirectly labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional ester. After normalization to total spots, the genes which background subtracted intensity did not exceed 2 SD above the mean blank were excluded. The data were then sorted to obtain genes differentially expressed by >or= 2 fold up or down in at least 5 of the 21 patients. RESULTS: In the 21 rectal cancer patients, 23 genes were up-regulated in at least 5 samples and 15 genes were down-regulated in at least 5 patients. Hierachical cluster analysis classified the patients into two groups according to the clinicopathological stage, with one group being all above stage II and one group all below stage II. CONCLUSION: The up-regulated genes and down-regulated genes may be molecular markers of rectal cancer. The expression profiles can be used for classification of rectal cancer.
Controlled Case Report on the Surgical Treatment of Recurrent Rectal Cancer: The Role of the Minimally Invasive Approach
Abstract(1) Background: The aim of this study is to investigate the diagnostic-therapeutic problem of pelvic recurrence of rectum cancer, highlighting current surgical standards and the possible role of the minimally invasive approach. This retrospective analysis of our surgical case study wishes to enter this debate while suggesting a possible line of action, based on the site of recurrence; (2) Methods: We examined, retrospectively, all the patients diagnosed, between 2008 and 2018, with cancer of the rectum at the &quot;Pietro Valdoni&quot; Department of Surgery and monitored their follow-up for 5 years. The sample consisted of 368 patients with rectal neoplasm, 136 females and 232 males, with an average age of 65.8 (ranging from 37 to 86); (3) Results: In 103 of the cases, the neoplasm was located in the upper rectum (28%), in 119 cases in the middle rectum (32.3%), in 102 cases in the lower rectum (27.7%), in 31 cases (8.4%) at the level of the right/sigma junction and in 13 cases it was not possible to define the site with certainty (3.5%); (4) Conclusions: The discussion re-mains open as to which approach is best at surgical level, whether laparoscopic, robotic or open-air. Our experience informs us that the most dangerous site remains on the anastomotic site.
Minimally invasive treatment in early rectal carcinoma
AbstractRadiotherapy alone and local excision combined with radiotherapy have been alternative treatments of early rectal carcinoma resection.Compared with radical surgery,both radiotherapy alone and local excision combined with radiotherapy can get satisfactory effect,and prevent the high rate of complications and adverse reactions,which will improve the quality of life for patients with rectal carcinoma and should be recommended.
Key words:
Rectal neoplasms; Radiotherapy; Local excision
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.
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.
